DOI: 10.1002/cphc.201402657

Articles

Computational Insights into the Charge Relaying Properties of b-Turn Peptides in Protein Charge Transfers Ru Zhang, Jinxiang Liu, Hongfang Yang, Shoushan Wang, Meng Zhang, and Yuxiang Bu*[a] Density functional theory calculations suggest that b-turn peptide segments can act as a novel dual-relay elements to facilitate long-range charge hopping transport in proteins, with the N terminus relaying electron hopping transfer and the C terminus relaying hole hopping migration. The electron- or holebinding ability of such a b-turn is subject to the conformations of oligopeptides and lengths of its linking strands. On the one hand, strand extension at the C-terminal end of a b-turn considerably enhances the electron-binding of the b-turn N terminus, due to its unique electropositivity in the macro-dipole, but does not enhance hole-forming of the b-turn C terminus because of competition from other sites within the b-strand. On the other hand, strand extension at the N terminal end of the b-turn greatly enhances hole-binding of the b-turn C terminus, due to its distinct electronegativity in the macro-dipole,

but does not considerably enhance electron-binding ability of the N terminus because of the shared responsibility of other sites in the b-strand. Thus, in the b-hairpin structures, electronor hole-binding abilities of both termini of the b-turn motif degenerate compared with those of the two hook structures, due to the decreased macro-dipole polarity caused by the extending the two terminal strands. In general, the high polarity of a macro-dipole always plays a principal role in determining charge-relay properties through modifying the components and energies of the highest occupied and lowest unoccupied molecular orbitals of the b-turn motif, whereas local dipoles with low polarity only play a cooperative assisting role. Further exploration is needed to identify other factors that influence relay properties in these protein motifs.

1. Introduction suitable redox relays, which serve as “stepping stones” within proteins. The role that peptide-bridging groups play in assisting charge transport in donor–acceptor complexes and proteins has been the subject of theoretical and experimental investigations.[3, 10] Charge hopping transport can be categorized as electron hopping or hole hopping, depending on the properties of the donor, acceptor, and bridges. Electron hopping requires that the relay be readily reduced so that it can capture an excess electron easily, whereas hole hopping requires that the relay be readily oxidized so that it can ionize to release an electron, and form a hole. An electron-accepting relay therefore promotes electron hopping transport, whereas an easily ionized intermediate facilitates hole hopping transport. Studies have revealed that several of the proteinogenic amino acid residues with sufficient electron affinities (EAs) can function as electron relays (e.g. protonated Arg, His, and Lys), and those with low ionization potentials (IPs) can serve as hole relays (e.g. Trp, Phe, and Tyr).[13–16] We believe that peptide configurations of sufficient electropositivity and electron-binding energy have the potential to mediate electron migration, and that those having the appropriate electronegativity and low electron-ionizing energy can facilitate long-range hole transfer. Recent results in our lab have verified that favorable bridging peptides for charge transfers could be common protein secondary structural motifs, such as the a helix, loop, and 310 helix in donor– bridge–acceptor charge-hopping systems.[17–19] We have found that a- and 310-helices can act as dual relay stations to support

Interest in long-range charge hopping transport in proteins has grown because of its significance in biological systems, synthetic processes, nanoscale materials, and other areas.[1–5] The mechanisms of charge migration in proteins have been investigated extensively by numerous researchers, and our understanding of them has become advanced in recent years. Despite controversy in this area, single-step super-exchange tunneling and multistep hopping have been demonstrated to be two general charge-transport mechanisms,[6–8] and the competition and transition between these, depending on the spacer distance variation, has been investigated by means of experiment and theoretical calculation.[9] At present, multistep hopping is considered to be a more efficient or predominant mechanism in long-range charge-transfer processes in proteins.[7, 10–12] In this mechanism, a charge transiently resides at a bridge for a short time (allowing for some nuclear relaxation) during its journey from one redox center to another. This intervening bridge, or medium, undergoes a change in redox state during the process and undoubtedly makes a significant contribution to long-range charge transport. Therefore, charge hopping transfer is strongly dependent on the presence of [a] R. Zhang, Dr. J. Liu, Dr. H. Yang, S. Wang, M. Zhang, Prof. Dr. Y. Bu Institute of Theoretical Chemistry School of Chemistry and Chemical Engineering Shandong University, Jinan, 250100 (P.R. China) E-mail: [email protected] Supporting Information for this article is available on the WWW under http://dx.doi.org/10.1002/cphc.201402657.

ChemPhysChem 2015, 16, 436 – 446

436

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles tors of charge hopping transfer events in proteins. In this work, we calculated electron affinities and ionizing potentials of b-turn oligopeptides [represented by MeCO-(NH-CH2-CO)n-NHMe, n = number of amino acids] to thermodynamically evaluate their potential to serve as electron or hole relays in charge hopping transfers, and to analyze spin density distributions of the corresponding anionic or cationic structures to identify where a charge prefers to reside transiently. Although there are many different types of b-turns in proteins,[26–28] we focus our discussion on hook structures with the type II b-turn, which is a common type of turning conformation, and also on type I’ b-turns, which is a more frequent type of turning conformation in b-hairpin structures.[30] Four types of b-turn oligopeptide backbones with different numbers of amino acids were modeled by neglecting all side chains to clarify which factors govern the relay properties in those structures using density functional theory (DFT) calculations. First, we considered a single bstrand, which is the basic unit of a b-sheet, to evaluate the role it plays in charge transfer processes in proteins. Next, a single bstrand was linked to the C or N terminus of a small b-turn motif to constitute the hook (I) or hook (II) structures, respectively (Figure 1). Finally, an antiparallel b-pleated sheet fragment was linked to a simple b-turn motif to constitute a simple b-hairpin structure.[27, 29, 31] A general structure and the model b-turn oligopeptides are shown in Scheme 1 and Figure 1.

charge transfers in proteins, with the C and N termini serving as the hole relay and electron relay, respectively; their relaying properties are considerably different from each other due to their different hydrogen-bonding modes.[20, 21] In addition, peptide loops have also been demonstrated to be efficient electron relays in the bridge-assisted donor–acceptor pathways of protein charge transfers.[10, 19] Thus, we further envision that the b-turn configuration of oligopeptides, a special loop structure, might play an important role in mediating long-range charge transfer. However, it is unclear how the relaying properties of b-turn structures vary with changes in conformation, number of amino acids, or other factors. Because of the significance of b-turns for the biological functions of proteins, much effort has been devoted to the structures and properties of b -turn oligopeptides. In particular, experiments have demonstrated that hydrogen bonding in b-turn peptides can accelerate electron transfer in a donor–acceptor complex bridged by a b-turnforming depsipeptide.[22] Experiments and molecular modeling have also indicated that conformational flexibility controls the efficiency of proton transfer between reactive centers, and the b-turn is more flexible than the b-sheet motif.[4, 23–25] Thus, studies on the function and properties of b-turn structures involved in charge transport are extremely interesting for understanding charge-transfer mechanisms in proteins. In this work, we analyzed the EA, IP, and electron detachment energy (DE) of various neutral b-turn oligopeptides, and the spin density distribution (1) of their charged counterparts, to identify peptides that participate in, or as charge relays assist, long-range charge transfers, and to evaluate the influence of different peptide lengths and diverse conformations on the relay properties. Primarily, this study provides computational evidence that 1) a b-turn structure can be a novel and promising dual relay to facilitate long-range charge migration; 2) relay properties, such as electron-binding or -releasing abilities, positions, and so forth, are closely related to the structural diversity and length of the b-turn oligopeptides; 3) the large polarity of the macro-dipole of these b-turn structures plays a predominant role in determining relay properties, whereas local dipoles (each peptide motif), with small polarity, cooperatively assist long-range charge transfers.

All of the structures were optimized or calculated using the DFT method with Becke’s hybrid functional (B3LYP),[32, 33] and with the 6-31G(d) or 6-31 + + G(d,p) basis sets using the Gaussian 03 suite[34] of programs, respectively. Furthermore, the optimized

Figure 1. Two types of hook structures. Left: doubly H-bonded hook (I) and hook (II) structures. Right: singly H-bonded structures. Two H-bonds are formed between a carbonyl oxygen and two amino groups, single H-bonds are formed between a carbonyl oxygen and one amino group.

Calculations and General Considerations The b-turn structure is a fundamental secondary structure element and a common feature of proteins that involves four amino acids, hydrogen bonded between the i and i+3 residues;[22, 26–28] up to 25 % of all residues in folded proteins are involved in b-turns. Because a b-turn can change the direction of an amino acid arrangement and can boost the stability of a b-hairpin structure, it is often used for linking b-sheets in an antiparallel configuration, which is a feature of protein secondary structure and also a part of large peptide assemblies, and is further stabilized by interstrand Hbonds.[29] The simplest b-hairpin structure, in which the two antiparallel b-strands are linked by a short loop, especially a b-turn, is widely distributed in fibrous (e.g. fibroin) and globular proteins. Because these motifs link diverse secondary structures and constitute active redox centers, we believe that they are not just scaffolds supporting the protein conformation, but are also efficient media-

ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

Scheme 1. The structure of a b-turn oligopeptide. Linking a b-strand to the C terminus of the turn forms hook (I) structure. Extension of the N terminus of the turn forms the hook (II) structure. Linking a b-strand to each of the C and N termini gives a b-hairpin structure. See also Figure 1.

437

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles structures were validated by performing harmonic vibrational analyses to confirm the minima.

relaying abilities. An excess electron cannot be trapped readily by a short tetrapeptide b-strand, as evidenced by negative values of VEA ( 0.01 eV) and AEA ( 0.19 eV). This is because the weak polarity of the macro-dipole determined that the N terminus has such low electropositivity that it has no capacity to attract an excess electron. However, the VEA and AEA values for this series of structures increase persistently as the oligopeptide length increases, and even become positive as the strand extends (e.g. VEA = 0.19–0.49 eV and AEA = 0.05– 0.19 eV for long strands where n = 6–14), which indicates that a long b-strand can vertically or adiabatically capture an excess electron and the electron-capturing ability is enhanced constantly with the strand extension. The increasing polarity of the macro-dipole results in the raised electropositivity of the N terminus. Furthermore, the increase of VEA becomes slow at n > 8 compared to n < 8, as shown by a gradually increasing curve with respect to the strand length, owing to the local dipole effect[19] (Figure 2). This is because the newly added local dipoles weakly contribute to the overall polarity of the macro-dipole in a long b-strand. Thus, the electropositivity of the N terminus is enhanced more and more gradually in long strands, which results in EA enhancement occurring more and more gradually in this process. Spin density distributions of the relaxed anionic b-strand structures were examined to evaluate the suitability and positions of electron binding sites in b-pleated strands. Inspection of the spin densities reveals that an excess electron is almost completely localized at an N-terminal dipeptide motif in a short b-strand (n = 5) due to the driving force of a macrodipole, verifying that the positive N terminus can provide a suitable site for an excess electron to reside transiently. However, as the number of amino acids increases, spin density distributes over diffuse p*(CONH) orbitals of other peptide units adjacent to the C terminus of b-strand, although a large percentage of the spin density remains localized at the N terminus (Figure 1). It is conceivable that favorable local polarity imparts electron binding ability to those folded regions. With strand extension, spin density distribution over those diffuse p*(CONH) orbitals has a tendency to gradually increase, as evidenced by spin density distributions at the N terminus (0.84, 0.84, 0.76,

2. Results and Discussion To further understand the possibility and suitability of a b-turn structure to serve as a charge relay for long-range charge hopping transfer in proteins, we considered four different b-turn oligopeptide sequences (Scheme 1 and Figure 1): 1) single bpleated strand; 2) hook (I) structure formed by linking a single b-strand to the C terminus of a b-turn motif; 3) hook (II) structure formed by linking a single b-strand to the N terminus of a b-turn motif; 4) b-hairpin structure formed by linking an antiparallel b-sheet to a b-turn.

2.1. Single b-Pleated Strand 2.1.1. b-Strand N Terminus Serving as an Electron Relay This structure represents a rational model peptide chain derived from a b-sheet. Because a b-turn motif is usually linked to one or two b-strands, forming the b-turn oligopeptides in proteins, we speculated that the strand structure might influence the charge-relaying abilities and properties of a b-turn. Cooperative interaction of all local dipoles (CONH) generates a macro-dipole, with a positive-charge center at the N terminus and a negative-charge center at the C terminus. Calculations revealed that the total dipole moment of this structure increases linearly with the number of Gly residues, and the direction correlates well with the orientation of the carbonyl groups. Thus, the charge-binding abilities and positions of this configuration should be determined by the polarity and direction of the oligopeptide macro-dipole. It is clear that an excess electron prefers to reside at the electropositive N terminus of a bstrand, whereas a hole prefers to reside at the electronegative C terminus. To evaluate the electron-capturing ability of this kind of structure, we calculated the vertical electron affinity (VEA) and adiabatic electron affinity (AEA), which correspond to the energy released during vertical or adiabatic electronbinding processes and thus are proper indicators of electron-

Figure 2. Left: the dependence of VEA, AEA, IPA, and IPV of the b-strand structure on the number of amino acids. Right: the spin density distribution of relaxed anionic (top) or cationic (bottom) b-strand (n = 7).

ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

438

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles and 0.70, corresponding to the b-strand structures with 7, 9, 11, and 13 amino acids, respectively). Existence of the two distinct zones for electron capture in a b-strand oligopeptide is a result of cooperation between the macro-dipole and local dipoles. As the b-pleated strand structure contains a stretching peptide sequence, the effect of long-distance peptide interactions on the macro-dipole becomes weak and no longer sensitive to the length of the oligopeptide. The result is that the macro-dipole effect gradually intensifies in long strands and local dipole effects become dominant (although weak) in electron-relaying process. Therefore, b-strand extension has a minor effect on the overall polarity of macro-dipole in a long strand. In this case, regional dipoles that are distant from the N terminus and adjacent to the C terminus can also relay an excess electron, acting as an assisting residence and also as components of a macro-dipole. These phenomena related to spin densities can further intuitively explain why EA values increase gradually in long strands, as mentioned above. High polarity of the macro-dipole always plays a critical role in governing the overall relaying properties, whereas low polarities of regional dipoles can also give cooperative assistance by providing transient and weak electron-relaying sites. The lowest unoccupied molecular orbital (LUMO) of a neutral structure is located at the N terminus of the b-strand, which corresponds to the main spin density distribution of a relaxed anionic structure. Its energy ( 1.01 to 1.36 eV) decreases inversely with strand extension, a demonstration that the bstrand N terminus can provide a favorable unoccupied orbital with low energy for an excess electron to occupy transiently. Nonlinear correlation between the LUMO energy and the number of amino acids in a neutral structure is closely related to the variation trends of VEA and AEA. In short, the N terminus of a single b-strand can provide a site for an excess electron to reside temporarily at an electron relay, but its electron-capturing ability is not particularly strong because of the slightly low polarity of its macro-dipole.

ty of this series of strand structures to relay a hole. Trp has the smallest IP of the 20 types of universally genetically encoded amino acids and has been shown to be an effective hole relay in proteins.[16, 35, 36] Although vertical ionization potential (IPV = 8.5–7.8 eV) and adiabatic IP (IPA = 8.2–7.7 eV) values of bstrands decrease to the values of Trp (IPV = 7.43 eV, IPA = 7.15 eV) as the number of amino acids increases from three to 13 (Figure 2), they are sums of all functions of the main site and several other dispersed weak sites (HOMO at the C terminus and diffuse p(-CONH-) orbitals), rather than a result of a specific relay station. The ionizing ability of the C terminus is extremely weak because this specific site is not sufficiently electron-rich, due to the somewhat low polarity of macro-dipole. The extensive and diffuse pleated regions of the strand also have the potential to release an electron due to the effect of local polarity, and thus can contribute to the hole. Ultimately, collaboration of macro-dipole and local dipoles contributes to the extensive delocalization of a hole over the entire b-strand. In contrast to the helix structure, there is an optimum and unidirectional H-bond mode, which can considerably enhance the overall polarity of the macro-dipole in a b-strand. Thus, the total dipole moment does not only orientate with the entire peptides chain, but branches due to dispersive local dipoles, which also reduce the total polarity of the macro-dipole. These factors act together and give rise to a consequence that the C terminus of this strand is not more electron-rich than other local dipoles, and thus, it is impossible to form a hole that completely localizes around this site. Thus, the criteria for a hole relay within a macro-dipole are stricter than those of an electron relay in terms of large polarity, effective charge distribution, HOMO/LUMO energies, and so forth. The nonlinear variation of IPV and IPA with respect to the strand extension is further evidence of a local dipole effect in long peptide sequences (Figure 2). In brief, the hole-relaying ability of the C terminus in a bstrand is extremely weak due to the low polarity of the macrodipole and interference effects arising from extensive and dispersive local dipoles.

2.1.2. b-Strand C Terminus Acting as a Weak Hole Relay As the C terminus of a single b-strand is an electronegative center of a macro-dipole, we assumed that this site, with ionizing properties, can act as a relay to facilitate long-range hole migration, in the same manner as the corresponding site on an a helix. Orbital analysis reveals that the highest occupied molecular orbital (HOMO) is primarily located at the C terminus, which seems to support our hypothesis. Unexpectedly, after releasing an electron adiabatically, a hole is almost delocalized over the whole strand instead of only localizing at the C terminus, although the hole distribution on the C terminus is slightly more than that on other sites, as shown in Figure 2. This observation implies that the C terminus of a single bstrand struggles to be an effective hole relay, but it is possible to act as a weak or a potential hole relay by offering a specific and weakly electronegative site for a hole to reside transiently. The IP, as an important thermodynamic indicator, associated with energy consumption as an electron departs from a neutral structure, can be used to evaluate well the suitability and abiliChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

2.2. Hook (I) Structures For each hook structure, we selected two types of turn: a pure b-turn (a four-residue segment with an H-bond between i and i+3 residues), and another containing both a b-turn and an aturn (a five-residue fragment H-bonded between the i and i+4 residues and also cooperatively between the i and i+3 residues—an a,b-mixed turn), as shown in Figure 1. The former contains only one H-bond in the turn—a single H-bond mode, whereas the latter turn contains two H-bonds—a double Hbond mode; this is the most remarkable difference between the two types of hook (I) structures. 2.2.1. b-Turn N Terminus Serving as an Effective Electron Relay In the two types of hook (I) structures, the formation of one or two H-bonds considerably enhances the local polarity of the b439

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles electron migration, and this relaying ability can be enhanced through strand lengthening.

turn motif and leads to a strongly electropositive region at the b-turn N terminus. Cooperative interaction of all the local dipoles yields a macro-dipole in which the N terminus of the bturn motif is a strongly electropositive center that is perfectly consistent with the LUMO distribution. Thus, when an excess electron attaches to the structure, it prefers to reside at the electropositive b-turn N terminus. Spin density distributions of relaxed anionic structures reveal that an excess electron is almost completely localized at the N terminus of the b-turn motif (Figure 3), implying that the b-turn N terminus can act as an exclusive electron relay in the hook (I) structure. Similarly with the b-strand structure, AEA values of both series of hook (I) structures increase continually with strand extension due to the increase in polarity of the macro-dipole, and the variation becomes more incremental in longer structures, due to the local dipole effect (Figure 3). However, unlike the b-strand structure, AEA values of the hook (I) structures are significantly higher than b-strand structures with the same number of amino acids, particularly for double H-bonded hook (I) structures. These results also reveal that hook structures containing an a,b-mixed turn have a greater tendency to capture excess electrons than those only containing b-turns, as evidenced by the larger AEA values of the former hook (I) structures. These results suggest that the H-bond within the turn is a key factor that determines the electron-uptake ability, because it considerably improves the polarity of the macrodipole and the electropositivity of the b-turn N terminus, which can provide an electron-deficient site for an excess electron to reside in transiently. Thus, the double H-bond mode affords a macro-dipole of higher polarity than the single H-bond mode, as well conferring electron-relaying ability. Furthermore, the LUMO energies of neutral structures and singly occupied molecular orbital (SOMO) energies of the corresponding relaxed anionic structures both decrease with the number of amino acids, but do not vary linearly with respect to the extension of the hook (I) structure, which is consistent with the variation of EA. Therefore, the b-turn N terminus of this hook (I) structure can serve as an effective electron relay to facilitate long-range

2.2.2. Hole Relay in Hook (I) Structures To evaluate the ionizing ability of these hook (I) structures, we calculated the IPA value. For the simplest b-turn, IPA = 8.65 eV. Although it is larger than the IPA value of Trp (7.15 eV), it is low enough to potentially ionize the b-turn C terminus. The IPA values of both hook (I) structures (n = 4–14) decrease gradually as the strand lengthens—the ionizing ability is continually reinforced with extension of the strand (Figure 4). The IPA values of both hook (I) structures decrease sharply at n < 8 but less so after n > 8, a further demonstration of the local dipole effects in long structures. However, the IPA of a long (n > 6) double Hbond hook structure is clearly lower than that of the corresponding single H-bond hook structure. This observation indicates that a hook (I) structure containing both a- and b-turns (a,b-mixed turn) has a greater capacity to release an electron to assist long-range hole transfer than structures only containing b-turns. For double H-bond hook (I) structures, spin density distributions of relaxed cationic structures reveal that hole distributions are interestingly regular over structures of varying length. In the simplest b-turn motif, spin density is mainly localized at the C terminus of the b-turn (the second and third residues), which is the electronegative center of the macro-dipole, further implying that it could be a promising candidate as a hole relay station. However, as the number of amino acids is increased to four, six, and eight, a hole distributes over two spatially separate regions: one around the b-turn C terminus, and the other around the b-strand C terminus (a dipeptide unit; Figure 4). In addition, the fraction of spin density distributed on the b-turn C terminus decreases, whereas the distribution increases at the other site upon strand extension, as evidenced by 1 values of 0.50, 0.43, and 0.37 at the b-turn C terminus in hook (I) structures, in which n = 4, 6, and 8, respectively. This observation sufficiently demonstrates a competition between the two potential hole relaying sites (b-turn C terminus vs. b-

Figure 3. Left: a comparison of AEA values of two types of hook (I) structure and that of a b-strand. Right: spin density distribution of relaxed anionic octapeptide structure, as a representative of hook (I) structures (n = 4–12).

ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

440

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles

Figure 4. Left: a comparison of IPA values of the two types of hook (I) structure. Right: spin density distributions of relaxed cationic doubly H-bonded hook (I) structure (containing both a- and b-turns). The singly H-bonded hook (I) structure (containing only a b-turn) has a similar distribution.

to constitute a strong macro-dipole, and thus cannot only act in concert, but can also exert individual effects. As a result, the oligopeptide segment around the b-strand C terminus is not sufficiently electronegative to attract a residing hole, leading to an extensive and dispersive spin density distribution over the whole strand as well as the b-turn C terminus. However, the b-strand C terminus still plays a somewhat dominant role as a hole relay in mediating long-range hole hopping transport, and the b-turn C terminus and other scattered sites provide effective cooperative assistance in long hook (I) structures (n = 12, 14). In other words, the relay properties of this structure are mainly determined by two factors: the highly electron-rich zone—the b-strand C terminus—resulting from macro-dipole effect, and the much less electron-rich region— the b-turn C terminus—caused by local dipole effect. The spin density distribution of a single H-bond hook structure is similar to that of the double H-bond hook structure. The difference is that the electron-releasing ability of the C terminus of a b-turn within the single H-bond hook structure is weaker than in double H-bond hook (I) structure. Additional Hbonds resulting from an a-turn can further increase the electronegativity of the C terminus of a b-turn and improve the corresponding hole-relaying ability. Therefore, the b-turn C terminus in hook (I) structures can act as a hole relay to facilitate long-range hole migration, but its relaying ability is so weak that it can be severely influenced or even weakened further by competition from other sites. Although the b-turn C terminus is not the most efficient hole relay in this type of structure, its influence in determining hole-relaying abilities and positions cannot be dismissed for these hook (I) structures.

strand C terminus), and also reveals that the hole gradually transfers from the b-turn C terminus to b-strand C terminus as the strand extends. Therefore, the b-turn C terminus is a main relay for a hole to reside temporarily in small hook (I) structures (n = 4), whereas the b-strand C terminus is the hole site preferred to the b-turn C terminus if the number of amino acids is greater than four. As the strand extends, the electronegativity of the b-strand C terminus becomes stronger due to large polarity of the macro-dipole, and the electronegativity of the b-turn C terminus is offset by the electropositivity of the bstrand N terminus. As a result, the oligopeptide segment close to the b-strand C terminus is the strongest competitor to the b-turn C terminus for hole relaying due to its large capacity in ionizing and hole-forming, and its ability is even stronger than the b-turn C terminus site in hook (I) structures with more than nine amino acids. Furthermore, the HOMO consists of two delocalized p bonds formed by the two C-terminal residues of the b-strand, and its energy level increases considerably with strand lengthen, implying that the HOMO electron becomes unstable and is readily leaves. More interestingly, when the number of amino acids increases to 10, 12, and 14 in the hook (I) structure, spin density distributions of these relaxed cationic structures are different from that of short hook (I) structures. Unlike those structures, the spin densities of the longer structures are not specifically assigned to one or two particular sites, instead they are dispersive and delocalize over the whole strand (Figure 4). The HOMO localized at the bstrand C terminus is better able to release an electron and provide a site for a hole compared to other HOMO regions scattered over the protein. Although the b-strand C terminus remains an electronegative center within the macro-dipole, this property is at best comparable to other sites if the hook (I) structure contains a long strand (e.g. n = 12, 14), due to local dipole effects. For the same reason, the electronegativity of the b-turn C terminus is no longer distinct, and is even close to that of small, disperse, pleated sites. In a long hook (I) structure, the many local dipoles cannot couple together effectively ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

2.3. Hook (II) Structures 2.3.1. Electron Relay and Relay Properties As mentioned previously, the electropositive N terminus of the b-turn motif has the potential to act as an electron relay to fa441

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles It is clear that competition and cooperation between the two effective electron-relay sites contribute to the overall relaying properties of hook (II) structures. In double H-bond hook (II) structures, spin densities over the b-turn N terminus were 0.49, 0.38, 0.41, and 0.56 for n = 8, 10, 12, and 14, respectively, indicating that electron-capturing abilities of the two potential relay sites are not significantly different in this type of structure. Two reasons can account for why the b-turn N terminus in this structure can be a hope rival to compete with the bstrand N terminus in the electron-relaying process: one is the strong electropositivity of the b-turn N terminus caused by local dipole effects within the doubly H-bonded turning region, and the other is the gradual increase in, almost constant, electropositivity of the b-strand N terminus, which is determined by the macro-dipole effect. In other words, the existence of the two positive-charge centers in the relaxed structure results in two transient residences for an excess electron. However, in singly H-bonded hook (II) structures, although spin densities mainly distribute at two sites, as in the double Hbond mode, spin density over the b-turn N terminus is less than the other competitive site (e.g. n = 8; Figure 5). The difference between the two modes of hook (II) structures in relaying excess electrons should be due to the two different H-bond modes. Two H-bonds within a bFigure 5. Spin density distribution of anionic hook (II) structure (n = 8) before geometric relaxation and after relaxturn are better than a single Hation. Top: single H-bond mode (b-turn only). Bottom: double H-bond mode (a- and b-turns). bond for raising both the polarity of the macro-dipole and the excess electron, the b-strand N terminus can host a large part electropositivity of the N terminus. This phenomenon is also of it transiently due to the effect of the macro-dipole, and reflected in the different EA values of the two modes. As other diffuse sites (peptide bonds) on the strand can also shown in Figure 6, both VEA and AEA of double H-bond strucshare part of the excess electron for assistance due to the eftures are higher than those of single H-bond structures, implyfects of dispersive small local dipoles. The VEA values of these ing that the former has greater electron attraction than the hook (II) structures are in the range 0.27–0.57 eV (double Hlatter. As the structure extends in length to the 14-amino-acid bond mode) or 0.16–0.51 eV (single H-bond mode), and conhook (II) structure, as well as the majority of an excess electron tinually increase with strand extension due to the increasing residing at the two main sites, there is also a small portion of polarities of the macro-dipole; however, this rate of increase spin densities delocalized on the extensive and diffuse p* orbigradually subsides due to local dipole effects. Furthermore, getals over the whole strand. This reveals that some diffuse pleatometry relaxation can further stabilize the electron-bound ed parts on the strand can also share responsibility for binding motif, and the excess electron can adjust its temporary resithe excess electron, due to local dipole effects, and the effect dence to adopt a more stable state in the relaxation process. of the two centers become less important than that in shorter Inspection of spin densities of relaxed anionic motifs reveals strands of this structure. that the bound excess electron does not always occupy the bIn addition, we also compared the electron-binding ability of strand N terminus as it does before relaxation, but that some the hook (II) structure to that of hook (I); observations reveal move from their initial residence (the b-strand N terminus) to that at the same H-bond mode, the AEA of hook (I) is always the other positive site (the b-turn motif N terminus), as shown higher than that of the hook (II) structure with the same in Figure 5. Geometrical relaxation renders the b-turn N terminumber of amino acids, especially in the case of the double Hnus more positive and more attractive to an excess electron. bond mode (Figure 6, right). This implies that strand extension Consequently, two spatially remote spin-distributing regions of hook (I) structures can greatly improve the electron-binding appear—the b-strand N terminus (the last three residues) and ability, whereas strand extension of hook (II) structures can the b-turn N terminus (two residues)—and both have compaonly yield a smaller effect. The captured electron is stabilized rable abilities to capture an excess electron, as already shown. transiently at a single assigned occupation site in hook (I)

cilitate long-range electron transfer in proteins. In hook (II) structures, a b-strand is linked to the N terminus of a b-turn motif, constituting a new macro-dipole, which contains a positive center at the b-turn motif C terminus and a negative center at the b-strand N terminus. In addition, inspection of molecular orbitals reveals that the LUMO locates at the N-terminal dipeptide unit of the b-strand, offering a low-energy ( 1.28 to 1.36 eV) orbital for an excess electron to reside transiently. It cannot be overlooked that the b-turn N terminus is also somewhat electropositive due to the local polarity of the turning local dipoles, although slightly weaker than the bstrand N terminus. After an excess electron is taken up vertically by a hook (II) structure that is held in either the single or double H-bond mode, a large percentage of the excess electron distributes at the b-strand N terminus in a Rydberg-like state, and the remainder distributes over the whole strand in diffuse and extensive p* orbitals (Figure 5). Upon uptake of an

ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

442

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles

Figure 6. Left: a comparison of VEA or AEA values of the two types of hook (II) structure. Right: a comparison of AEA values of hook (I) and hook (II) structures.

structures, whereas an excess electron is assigned to two spatially distant regions with competition between them in hook (II) structures. This is mainly because the macro-dipole effect in hook (II) structures is severely weakened by competition between the two remote sites, whereas hook (I) structures always act as a macro-dipole by uniting all local dipoles, so that it can attract the whole excess electron to one assigned site, the b-turn N terminus. Thus, the N terminus of the b-turn motif can always act as a distinct electron relay to facilitate long-range electron hopping transfer in this hook (II) structure. Its ability is not particularly great, but neither is it unacceptably small. Ultimately, it becomes a comparable competitor to the other positive center within the b-strand.

long-range hole transfer as a hole relay. Observations revealed that the IPA gradually decreases as the strand is extended, implying that it is increasingly easy to lose an electron the longer the strand for this type of hook structure (Figure 7). The HOMO is located at the b-turn C terminus, consisting of two delocalized p bonds, and its energy increases constantly with strand lengthening. Similarly to those conformations discussed above, IPA and HOMO energies have a nonlinear correlation with the structure length, due to local dipole effects. Spin density distributions of relaxed cationic structures indicate that a hole is almost completely localized at the b-turn motif C terminus (a dipeptide unit) in short hook (II) structures (n = 4, 6), which further confirms the hole-relaying role played by the bturn C terminus. However, for hook (II) structures with more than six amino acids (n = 8, 10, 12, 4), there is also a small fraction of a hole that is delocalized over approximately three p bonds near the b-strand N terminus; most of the hole remains localized on the b-turn motif C terminus (Figure 7). That is primarily because cooperative interaction between spatially remote local dipoles gradually becomes weaker in long

2.3.2. b-Turn C Terminus Acting as a Hole Relay and Relay Properties In a hook (II) structure, the b-turn C terminus is always the electronegative center in the macro-dipole and can facilitate

Figure 7. Left: a comparison of IPA values of two types of hook (II) structure. Right: spin density distribution of two types of relaxed cationic hook (II) structures (n = 8).

ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

443

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles hook (II) structures. Residues remote from the b-turn motif N terminus can not only act as a portion of the macro-dipole, but also play a small but significant role as independent local dipoles. In addition, although the effects of those local dipoles are not particularly strong, they are not completely inactive in the hole-relaying process. Thus, the b-turn C terminus still plays a critically dominant role in hole-transport process. There are also some differences between the two H-bonding modes of hook (II) structures (Figure 7). Spin density over the b-turn C terminus in the double H-bond mode is slightly more than that for the single H-bond mode. The comparison between the two modes shows again that a slightly higher tendency for ionization arises from the former mode than the latter mode, with larger AEA of doubly H-bonded structures than values of singly H-bonded structures with the same number of amino acids (Figure 7). Furthermore, with strand extension, spin density over the C terminus of the b-turn decreases, which confirms that local dipoles distant from the turning region share more responsibility for transient hole capture. Therefore, it is the macro-dipole that always plays a predominant role in the hole-relaying process, whereas individual sites only give assistance cooperatively. Overall, the C terminal end of the b-turn motif in the hook (II) structure can act as an effective hole relay to release an electron and form a hole; this relaying ability is enhanced with extension of the N terminus strand.

Figure 8. Spin density distribution of the relaxed anionic (left) and cationic (right) forms of a representative b-hairpin structure (n = 6).

These phenomena indicate that geometry relaxation makes the b-turn N terminus become more positive and thus more attractive to an excess electron with a high preference over other sites, although the structure before relaxation has no strong attraction for an excess electron without a particularly powerful electropositive site. We have confirmed that properties of the LUMO are also related to electron deficiency, and thus are related to the relay positions and abilities in electrontransfer processes, as displayed by hook (I) structures. In the bhairpin structures, the LUMO always localizes at the b-turn motif N terminus and their energies are in the range 0.29 to 0.11 eV, higher than those of hook (I) structures ( 1.41 to 0.32 eV) with similar spatial distributions. This observation indicates that a b-hairpin structure can also provide a lowenergy orbital for an excess electron to reside transiently as in the hook (I) structure, although the energy of this unoccupied orbital is not especially low and thus cannot stabilize the captured excess electron, resulting in weaker electron-binding ability compared with the hook (I) structure. The weaker relaying ability of b-hairpins is also revealed by the fact that AEA values of hook (I) structures are obviously higher than those of the b-hairpin structures (Figure 9), which is attributed to the different electropositivity of the b-turn N termini in different macro-dipoles. Because of the low polarity of the macrodipole, the b-hairpin structure has a weaker electropositive center at the b-turn N terminus than that of the hook (I) structure, and thus has a lower EA. In these b-hairpin structures, AEAs increase with extension of the b-hairpin strand, but

2.4. b-Hairpin Structures After a discussion of the responsibility of the b-turn motif for relaying charges in two types of hook-like structures, it is natural to extend this to more complex b-hairpin structures. Notably, we selected the type I’ b-turn oligopeptides to investigate the relaying properties of the b-turn in the most common type of b-hairpin structures, in which the b-turn is more frequently of type I’ or II’.[30] 2.4.1. b-Turn N Terminus Acting as an Electron Relay Inverse arrangements of the two-strand peptide sequences render the system highly antisymmetric, resulting in hairpin structures with dipole moments that are considerably smaller than those of hook structures. Consequently, the polarity of the macro-dipole is extremely small. Although the excess electron is not always resident at the N terminus of the b-turn motif (it can reside at two sites, see the Supporting Information) at the moment of its capture, due to the low polarity of the macro-dipole, spin density distributions of relaxed anionic structures (Figure 8) reveal that an excess electron almost completely localizes at the N terminus of the b-turn motif, implying that an excess electron is drawn to reside at one assigned site after geometry relaxation. The AEA values of this series of structures are in the range 0.108–0.244 eV; these moderate values indicate that the hairpin structures are equipped to capture an excess electron adiabatically but their affinity is not so strong that the captured electron can depart the transient site of residence readily, thus they are excellent electron relays. ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

Figure 9. A comparison of IPA values of b-hairpin and hook (II) structures (bturn only), and comparison of AEA values of b-hairpin and hook (I) structures (b-turn only).

444

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles weak ability is the low polarity of macro-dipole in the b-hairpin structure.

dipole moments do not show a similar trend. That is because the electropositivity of one assigned site is determined more effectively by polarity rather than by the macro-dipole moment. Therefore, there is no direct relationship between EA and dipole moment in these special b-hairpin structures because of the directional diversity of local dipoles caused by conformational complexity. The b-turn N terminus plays a dominant role in relaying an excess electron in this type of b-hairpin structure through its electropositivity, but its capacity to relay an excess electron is neither strong nor slightly weak, because of the low polarity of the macro-dipole.

3. Conclusions In summary, our DFT calculations suggest a possibility for longrange electron or hole hopping transport in proteins via the N or C terminus of a b-turn structure, respectively, which act as novel charge-relay elements. The formation of an H-bond in a turning region is the most important factor to contribute to the polarity of macro-dipole or local dipole, as well as the electronic properties of the b-turn that has an electropositive N terminus and an electronegative C terminus. Indeed, electron- or hole-binding abilities of the two termini are neither strong nor weak in a simple b-turn structure, but represent a favorable basis for its relaying ability. On the one hand, the electron-relaying ability of the b-turn N terminus can be greatly enhanced with extension of the strand in hook (I) structures, due to its exclusive and powerful electropositivity in the highly polar macro-dipole. By contrast, in hook (II) structures, the electron-relaying role played by the b-turn N terminus is not as dominant as that in hook (I), because other sites within the strand also have the capability to provide transient sites for a portion of an excess electron. On the other hand, the holerelaying abilities of the b-turn C terminus in two hook structures are also greatly different. For the hole relay, the b-turn C terminus in hook (II) structures has a stronger ionizing ability than that in hook (I). This is because the b-turn C terminus in the former is always the electronegative center in a macrodipole with high polarity and always acts as an exclusive and effective hole relay, whereas that of the latter can be severely affected by competition from the C terminus of the linked bstrand. Thus, as demonstrated for the b-hairpin structures, electron- or hole-binding abilities of both termini of the b-turn motif degenerate compared with those of the two hook structures, due to the lowering of polarity of its macro-dipole by the extension with two strands at the two termini. The b-turn C terminus can only play a weak role in mediating hole hopping migration in the b-hairpin structure. It is also confirmed that the requirements for a qualified hole relay within a macrodipole are stricter than those for an electron relay in terms of polarity, effective charge distribution, HOMO/LUMO energy, and so forth. Furthermore, the charge-relaying ability of these structures improves with strand extension, but this is not a linear correlation because of local dipole effects. In other words, a b-turn structure can act as a novel dual charge relay and the relay properties are closely correlated with diverse conformations and branch strand lengths, which can considerably modify the polarities of the macro-dipole or local dipoles, as well as the cooperative interacting mode between them. In general, the high polarity of a macro-dipole always plays a predominant role in determining charge relay properties, whereas those local dipoles with low polarity only play an assisting role in facilitating long-range charge transfer in proteins, cooperatively. Indeed, the relay properties of such protein motifs are also affected by other factors, such as types and stretching range of the two chains, the redox potential between the

2.4.2. Hole-Relaying Properties of b-Turn C Terminus To further clarify what role a b-turn plays in hole hopping transfer in a simple b-hairpin structure, we calculated its IPA, and analyzed the corresponding hole distributions of relaxed cationic structures. The calculations reveal IPA values are in the range 8.408–7.835 eV, and decrease as the number of amino acids is increased. These values are comparable with those of hook (II) structures, in which the b-turn C terminus can act as an effective hole relay to facilitate long-range hole migration, as discussed above. The IPA of a b-hairpin structure is always larger than that of singly H-bonded hook (II) structure with the same number of amino acids (Figure 9), implying that the C terminus of a b-turn motif within the b-hairpin structure has a lower capacity for releasing an electron and forming a hole than that of a hook (II) structure. Unlike the case of hook (II), spin density distributions of relaxed cationic structures do not always localize at the C terminus of a b-turn, but instead distribute over other electropositive sites of an extended strand, as shown in Figure 8. The C terminus of a b-turn plays a dominant role in electron-releasing process and many factors are responsible for this observation. The principal factor is the low polarity of the macro-dipole, caused by arrangement of two antiparallel peptide strands. The C terminus of the b-turn motif has no greater tendency for ionization than other electropositive sites because the electron-rich property of this site is not obvious. Consequently, spin densities can also distribute at two electropositive sites rather than localize at one assigned site after losing an electron adiabatically. Observation also revealed that the HOMO of a b-hairpin structure is not always localized at the C terminus of a b-turn as in hook (II) structures, but sometimes localizes in the C terminus of a b-turn (n = 6, 10), and sometimes at another site within the extended strand (n = 4, 8, 12; Supporting Information). It can also explain why the C terminus of a b-turn has insufficient capability to ionize and form a unique hole itself. The electron on the C terminus of a b-turn is not active enough to depart from this site and hop to other sites, and thus its hole-relaying ability is not prominent in the b-hairpin structures. Thus, the hole relaying ability of the b-turn C terminus degenerates slightly in this simple b-hairpin structure compared with other hook structures, which is due to interference from other potential sites. The most fundamental reason for its ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

445

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Articles donor and acceptor sites, other amino acid competition, capping effects, the dielectric environment, and so forth. Clearly, this work also serves as an impetus for further experimental and theoretical studies.

[20] X. Chen, L. Zhang, L. Zhang, W. Sun, Z. Zhang, H. Liu, Y. Bu, R. I. Cukier, J. Phys. Chem. Lett. 2010, 1, 1637 – 1641. [21] M. Zhang, J. Zhao, H. Yang, P. Liu, Y. Bu, J. Phys. Chem. B 2013, 117, 6385 – 6393. [22] D. A. Williamson, B. E. Bowler, J. Am. Chem. Soc. 1998, 120, 10902 – 10911. [23] D. Pogocki, E. Ghezzo-Schçneich, C. Schçneich, J. Phys. Chem. B 2001, 105, 1250 – 1259. [24] F. Huang, W. M. Nau, Angew. Chem. Int. Ed. 2003, 42, 2269 – 2272; Angew. Chem. 2003, 115, 2371 – 2374. [25] M. Marazzi, U. Sancho, O. CastaÇo, W. Domcke, L. M. Frutos, J. Phys. Chem. Lett. 2010, 1, 425 – 428. [26] P. Y. Chou, G. D. Fasman, J. Mol. Biol. 1977, 115, 135 – 175. [27] T. S. Haque, S. H. Gellman, J. Am. Chem. Soc. 1997, 119, 2303 – 2304. [28] J. A. Cuff, M. E. Clamp, A. S. Siddiqui, M. Finlay, G. J. Barton, Bioinformatics 1998, 14, 892 – 893. [29] M. Ramrez-Alvarado, T. Kortemme, F. J. Blanco, L. Serrano, Bioorg. Med. Chem. 1999, 7, 93 – 103. [30] B. L. Sibanda, T. L. Blundell, J. M. Thornton, J. Mol. Biol. 1989, 206, 759 – 777. [31] B. L. Sibanda, J. M. Thornton, Nature 1985, 316, 170 – 174. [32] X. Y. Pan, V. Sahni, Int. J. Quantum Chem. 2010, 110, 2833 – 2843. [33] S. M. Valone, J. Am. Chem. Soc. 2010, 132, 11387 – 11388. [34] Gaussian 03 (Revision E.01), M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, . Farkas, D. K. Malik, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashecko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian Inc., Wallingford CT, 2004. [35] J. Stubbe, D. G. Nocera, C. S. Yee, M. C. Chang, Chem. Rev. 2003, 103, 2167 – 2202. [36] C. Shih, A. K. Museth, M. Abrahamsson, A. M. Blanco-Rodriguez, A. J. Di Bilio, J. Sudhamsu, B. R. Crane, K. L. Ronayne, M. Towrie, A. Vlcˇek, Science 2008, 320, 1760 – 1762.

Acknowledgements This work was supported by the NSFC (21373123, 20633060, and 20973101) and the NSF (ZR2013BM027) of Shandong Province. Some of the calculations were carried out at the National Supercomputer Center in Jinan, the Shanghai Supercomputer Center, and the High-Performance Supercomputer Center at SDU-Chem. Keywords: charge relay · density functional theory calculations · ionization potential · spin density distribution · bturn oligopeptides [1] R. S. Clegg, J. E. Hutchison, Langmuir 1996, 12, 5239 – 5243. [2] H. B. Gray, J. R. Winkler, Annu. Rev. Biochem. 1996, 65, 537 – 561. [3] E. Petrov, Y. V. Shevchenko, V. Teslenko, V. May, J. Chem. Phys. 2001, 115, 7107 – 7122. [4] H. Yang, G. Luo, P. Karnchanaphanurach, T.-M. Louie, I. Rech, S. Cova, L. Xun, X. S. Xie, Science 2003, 302, 262 – 266. [5] X. Chen, C. Hao, J. Am. Chem. Soc. 2008, 130, 8818 – 8833. [6] D. Beratan, S. Skourtis, Curr. Opin. Chem. Biol. 1998, 2, 235 – 243. [7] T. Morita, S. Kimura, J. Am. Chem. Soc. 2003, 125, 8732 – 8733. [8] M. Cordes, B. Giese, Chem. Soc. Rev. 2009, 38, 892 – 901. [9] J. Vura-Weis, S. H. Abdelwahed, R. Shukla, R. Rathore, M. A. Ratner, M. R. Wasielewski, Science 2010, 328, 1547 – 1550. [10] R. A. Malak, Z. Gao, J. F. Wishart, S. S. Isied, J. Am. Chem. Soc. 2004, 126, 13888 – 13889. [11] S. Sek, A. Sepiol, A. Tolak, A. Misicka, R. Bilewicz, J. Phys. Chem. B 2004, 108, 8102 – 8105. [12] M. Choi, S. Shin, V. L. Davidson, Biochemistry 2012, 51, 6942 – 6949. [13] S. Delaney, J. K. Barton, J. Org. Chem. 2003, 68, 6475 – 6483. [14] C. Wittekindt, M. Schwarz, T. Friedrich, T. Koslowski, J. Am. Chem. Soc. 2009, 131, 8134 – 8140. [15] S. S. Isied, M. Y. Ogawa, J. F. Wishart, Chem. Rev. 1992, 92, 381 – 394. [16] M. J. Bollinger, Jr., Science 2008, 320, 1730 – 1731. [17] Y.-g. K. Shin, M. D. Newton, S. S. Isied, J. Am. Chem. Soc. 2003, 125, 3722 – 3732. [18] J. Watanabe, T. Morita, S. Kimura, J. Phys. Chem. B 2005, 109, 14416 – 14425. [19] B. Han, X. Chen, J. Zhao, Y. Bu, Phys. Chem. Chem. Phys. 2012, 14, 15849 – 15859.

ChemPhysChem 2015, 16, 436 – 446

www.chemphyschem.org

Received: September 22, 2014 Published online on November 27, 2014

446

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Computational insights into the charge relaying properties of β-turn peptides in protein charge transfers.

Density functional theory calculations suggest that β-turn peptide segments can act as a novel dual-relay elements to facilitate long-range charge hop...
979KB Sizes 1 Downloads 7 Views