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Journal of Biomolecular Structure and Dynamics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tbsd20
Theoretical Account of the ‘Spine of Hydration’ in the Minor Groove of Duplex d(CGCGAATTCGCG) a
a
P. S. Subramanian , S. Swaminathan & D. L. Beveridge
a
a
Chemistry Department Hall-Atwater Laboratories , Wesleyan University , Middletown , CT , 06457 Published online: 21 May 2012.
To cite this article: P. S. Subramanian , S. Swaminathan & D. L. Beveridge (1990) Theoretical Account of the ‘Spine of Hydration’ in the Minor Groove of Duplex d(CGCGAATTCGCG), Journal of Biomolecular Structure and Dynamics, 7:5, 1161-1165, DOI: 10.1080/07391102.1990.10508553 To link to this article: http://dx.doi.org/10.1080/07391102.1990.10508553
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [Purdue University] at 14:08 17 January 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions
Journal of Biomolecular Structure & Dynamics, JSSN 0739-1102 Volume 7, Issue Number 5 (1990), ®Adenine Press (1990).
Theoretical Account of the 'Spine of Hydration' in the Minor Groove of Duplex d(CGCGAATTCGCG)
Downloaded by [Purdue University] at 14:08 17 January 2015
P.S. Subramanian, S. Swaminathan and D.L. Beveridge Chemistry Department Hall-Atwater Laboratories Wesleyan University Middletown, CT 06457 Abstract The hydration ofB-form DNA involves a novel sequence of ordered water molecules in the minor groove known as the spine of hydration. The positions of the ordered waters in the AATT region have been determined and indicate water bridges between the A-N3 and T-02 acceptor sites. Theoretical calculation on hydration based on Monte Carlo simulation show that the water bridges are more sensitive to the prescription for intermolecular potentials than the choice of canonical vs. crystallographic geometry. The G ROM OS force field and the SPC model for water are shown to give an accurate theoretical account of the experimental data.
Hydration is well-known to be a critical determinant in the conformational stability of DNA ( 1). The nature of DNA hydration has been partially revealed from the ordered water positions in the crystal structures of duplex oligonucleotides (2). The crystal structure of d(CGCGAATICGCG) (3-9) has featured a sequence of ordered water molecules in the AATI region of the minor groove which has come to be known as the "spine of hydration" (6) and has been implicated in the preferential stability ofB-form DNA at high humidity (6,9). The base pairs in the crystallographic d(CGCGAATICGCG) exhibit a distinct propeller twist, which positions the hydrogen bond accepting atoms A-N3 and T-02 in the minor groove at ca. 3.7 A apart. The water molecules hydrating the nucleic acid atoms along the floor of the minor groove in the crystal structure are seen to be bridging these positions. The hydration of a canonical B-form of d(CGCGAATTCGCG) has recently been the subject of Monte Carlo simulations from this laboratory (10,11). Using proximity analysis and graphical presentations of hydration density, the nature of the hydration has been described. The calculations confirm the presence of an ordered water structure in the minor groove, but predict itto extend beyond the AATI region in the CGCG flanking sequences as well, thus extending throughout the minor groove of the B-form oligonucleotide. The major groove hydration features essentially saturation of hydrophilic sites and hydrophobic hydration around the T-CH3. The calculated backbone hydration consists of triads of water assembled into" cones of hydration" around the phosphates. The calculated patterns of hydration are generally consistent
1161
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Subramanian eta/.
with crystallographic and spectroscopic studies of nucleic acid hydration.
Downloaded by [Purdue University] at 14:08 17 January 2015
A specific discrepancy between the calculated hydration sites and the ordered water positions observed crystallographically was in the floor of the minor groove. Here the initial calculations (10,11) turned up monodentate hydrogen bonding to the acceptor atoms in the plane of the base pairs as opposed to A-N3 ...W...T-02 water bridges. There are two possible origins of this problem. One is in the choice of the canonical B form of DNA as a basis for the simulation studies. The second is the prescription chosen for the calculation of the intermolecular interaction energies, involving AMBER 3.0 charges (12) on the DNA atoms and the TIP4P water model (13). Subsequent studies, described herein, have been initiated to clarify the situation. We first carried out a Monte Carlo simulation completely analogous to that reported earlier, but assuming the crystal structure of the native dodecamer (3,4) rather than the canonical B form for the dodecamer. The calculation involved a screened charge model for d(CGCGAATTCGCG) together with 1951 water molecules (an excess of two hydration shells) in a hexagonal prism central cell under periodic boundary conditions. The volume of the system was taken to be consistent with an environmental density of 1 gm/cm 3 and the temperature was assumed as 298°K. The nucleic acid/water energy functions were taken to be AMBER 3.0/TIP4P. The simulation was carried out for an equilibration period of3000Kconfigurations, and the analysis was based on a production segment of lOOOK configurations. The average energy and other diagnostics in the simulation was seen to be stable over this segment of the realization. The calculated hydration density for the minor groove of the dodecamer from this simulation is shown in Figure 1, depicted for presentation here as the linear superposition of points representing oxygen coordinates of the solvent waters from a series of individual configurations taken at equally spaced intervals along the production segment of the realization. The clustering of such points is indicative of the position and localization of calculated hydration sites. The results of this simulation, as in the previous simulation assuming the canonical B form, predict sequential, monodentate hydrogen bonding in the AATT region coincident with the planes of the base pairs and are frame-shifted from the observed ordered water positions (large spheres in Figure 1), and do not account for the A-N3 ...W...T-02 water bridges observed in the crystal structure. We subsequently configured a completely independent Monte Carlo simulation based on the native dodecamer structure and 2106 water molecules, with an environmental density ofl gm/cc and a temperature of298°K. The potential functions used to describe the intermolecular interactions were based on GROMOS parameters for the DNA ( 14) and the SPC model for water ( 15). This calculation was carried out on a molecular simulation program developed by Swaminathan ( 16) with extensive modification and additional vectorization from GROMOS (14). Fully anionic phosphates and 22 Na + counterions were included. Spherical cutoffs were applied to all potentials with a switching function feathering the interaction energy to zero between 7.5 and 8.5 A. The cut-offwas applied on a group-by-group basis. The size
Downloaded by [Purdue University] at 14:08 17 January 2015
Spine of Hydration in CGCGAATTCGCG
1163
Figure 1: Calculated first shell hydration density in the minor groove of the native crystallographic form of d(CGCGAATICGCG) based on AMBER 3.0 charges for nucleic acid atoms and hte TIP4P model for water, presented as a superposition ofwateroxygen positions from 19 snapshots of equally spaced intervals along the lSOOK Monte Carlo realization. Large oepn circles are the position of the crystallographic ordered water comprising the observed spine of hydration (6).
of the hexagonal prism unit was chosen so that all solute-solvent interactions die off within the central cell. The calculations were carried out on a CRAY YMP at the Pittsburgh Supercomputer Center at a much improved sampling rate of 2300K configurations/hr. and involve lO,OOOK equilibration steps and lO,OOOK configurations of production. The results of the GROMOS/SPC Monte Carlo simulation on the hydration density in the minor groove of the dodecamer are shown in Figure 2. The calculated localizations ofhydration density are seen to coincide almost perfectly with the four experimentally determined positions. In particular along the floor of the AATT region of the minor groove, the most populous region ofhydration density corresponds to the position of the best determined crystallographic water and the lowest temperature factor. The interface between the GC and AT tracts in the sequence features a paucity of hydration density, consistent with the ideas about disruption of the spine advanced by Dickerson and coworkers (9). There is however considerable localization of hydration density in the GC tracks, expanding into a double ribbon
Downloaded by [Purdue University] at 14:08 17 January 2015
1164
Subramanian et a/.
I
•,.
Figure 2: Calculated first shell hydration density in the minor groove of d(CGCGAATTCGCG) based on GROMOS charges for the nucleic acid and the SPC model for water, based on a superposition of 40 structures. See caption to Figure I for further details.
motif as the minor groove widens toward the ends. This is consistent with observations on GC hydration in a recent crystal structure on a related sequence by Prive et al. (17). In summary, we find on the basis of two additional Monte Carlo simulations on the hydration of d(CGCGAATTCGCG) that the discrepancy with experiment observed for the ordered water positions along the floor of the minor groove in the spine of hydration is apparently due not only to our choice of the canonical rather than crystallographic form as a reference, but either to the prescription chosen for the intermolecular potential functions or the indirect effects involving electrostatics of the phosphates. The former is the more likely explanation, since the direct hydrogen bonding interactions of water molecules with groove atoms are expected to be dominant over long range indirect effects. The results are seen to be sensitive to the description of configurational energy. The GROMOS 12-6-1 non-bonded parameters and SPC model for water are shown in a simulation of considerable length to give a nearly perfecttheoretical account of the observed crystallographic ordered water positions in the spine of hydration.
Spine of Hydration in CGCGAATTCGCG
1165
Good agreement between calculated and observed water structure in related systems a and ~-cyclodextrine [18) and dCpG/proflavine [19) has also been reported based on the G ROMOS/SPC prescription for intermolecular potentials. Establishing an accurate theoretical account of the observed hydration structure is an important step in the validation of molecular simulation applied to nucleic acid systems.
Downloaded by [Purdue University] at 14:08 17 January 2015
Acknowledgments This research was supported by grants to DLB from the National Institutes of Health (GM-37909) and the National Science Foundation (CHE-8696117), and the Office ofN aval Research (N -00014-87-K-0312). Support from the Bristol Myers Corporation via a Connecticut Cooperative High Technology Research and Development Grant is also gratefully acknowledged. Access to the CRAYYMP for processing these calculations was provided by the National Science Foundation and the Pittsburgh Supercomputer Center. References and Footnotes
l. W. Saenger, Principles of Nucleic Acid Structure, Springer Verlag, New York (1983). 2. For a recent review, see E. Westhof and D.L. Beveridge in "Water Science Reviews, Vol. Ill, F. Franks, ed., Cambridge University Press, in press. 3. R.M. Wing, H.R. Drew, T. Takano, C. Broka, S. Tanaka and R.E. Dickerson, Nature 278, 755 (1980). 4. H.R. Drew, R.M. Wing, T. Takano, C. Broka, S. Tanaka, K. Itakure and R.E. Dickerson, Proc. Nat/. Acad. Sci. USA 78,2179 (1981). 5. R.E. Dickerson and H.R. Drew,J Mol. Bioi. 149,761 (1981). 6. H.R. Drew and R.E. Dickerson,!. Mol. Bioi. 151,535 (1981). 7. H.R. Drew, S. Samson and R.E. Dickerson, Proc. Nat/. Acad. Sci. USA 79, 4040 ( 1982). 8. AV. Fantini, M.L. Kopka, H.R.Drew and R.E. Dickerson,!. Bioi. Chern. 257,14868 (1982). 9. M.L. Kopka, AV. Fratini, H.R. Drew and R.E. Dickerson, J. Mol. Bioi. 163, 129 (1983). 10. P.S. Subramanian, G. Ravishanker and D.L. Beveridge, Proc. Nat/. Acad. Sci. USA 85, 1836 (1988). 11. P.S. Subramanian and D.L. Beveridge,! Biomol. Str. Dyn. 6, 1093 (1989). 12. S.J. Weiner, P.A. Kollman, D. Case, U.C. Singh, C. Ghio, G. Alagona, S. Profata and P. Weiner,!. Am. Chern. Soc. 106, 765 (1984). 13. W.L. Jorgensen, J. Chandrasakar, J. Madura, R.W. Impey and M.L. Klein, J. Chern. Phys. 79, 926 (1983). 14. W.F. van Gunsteren and H.J.C. Berendsen, GROMOS: Groningen Molecular Simulation System, University ofGroningen (1988). 15. H.J.C. Berendsen, J.P.M. Postma, W.F. van Gunsteren and J. Harmons, in Intermolecular Forces, B. Pullman, ed., Reidel, Drodrect, The Netherlands, 331 (1981). 16. S. Swaminathan, WESMOS: Wesleyan Molecular Simulation System, Wesleyan University (1989). 17. R.E. Dickerson, inStructure&Methods, Vol.3: DNA& RNA, eds., R.H. Sarma and M.H. Sarma, 001038, Adenine Press, Guilderland, N.Y. (1990). 18. J.E.H. Koehler, W. Saenger and W.F. van Gunsteren, Eur. J. Biophys. 15, 197 (1987). 19. S. Swaminathan, D.L. Beveridge and H.M. Berman,! Phys. Chern., in press (1990). Date Received: September 18,1989
Communicated by the Editor R.H. Sarma
Journal of Biomolecular Structure and Dynamics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tbsd20
Theoretical Account of the ‘Spine of Hydration’ in the Minor Groove of Duplex d(CGCGAATTCGCG) a
a
P. S. Subramanian , S. Swaminathan & D. L. Beveridge
a
a
Chemistry Department Hall-Atwater Laboratories , Wesleyan University , Middletown , CT , 06457 Published online: 21 May 2012.
To cite this article: P. S. Subramanian , S. Swaminathan & D. L. Beveridge (1990) Theoretical Account of the ‘Spine of Hydration’ in the Minor Groove of Duplex d(CGCGAATTCGCG), Journal of Biomolecular Structure and Dynamics, 7:5, 1161-1165, DOI: 10.1080/07391102.1990.10508553 To link to this article: http://dx.doi.org/10.1080/07391102.1990.10508553
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [Purdue University] at 14:08 17 January 2015
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions
Journal of Biomolecular Structure & Dynamics, JSSN 0739-1102 Volume 7, Issue Number 5 (1990), ®Adenine Press (1990).
Theoretical Account of the 'Spine of Hydration' in the Minor Groove of Duplex d(CGCGAATTCGCG)
Downloaded by [Purdue University] at 14:08 17 January 2015
P.S. Subramanian, S. Swaminathan and D.L. Beveridge Chemistry Department Hall-Atwater Laboratories Wesleyan University Middletown, CT 06457 Abstract The hydration ofB-form DNA involves a novel sequence of ordered water molecules in the minor groove known as the spine of hydration. The positions of the ordered waters in the AATT region have been determined and indicate water bridges between the A-N3 and T-02 acceptor sites. Theoretical calculation on hydration based on Monte Carlo simulation show that the water bridges are more sensitive to the prescription for intermolecular potentials than the choice of canonical vs. crystallographic geometry. The G ROM OS force field and the SPC model for water are shown to give an accurate theoretical account of the experimental data.
Hydration is well-known to be a critical determinant in the conformational stability of DNA ( 1). The nature of DNA hydration has been partially revealed from the ordered water positions in the crystal structures of duplex oligonucleotides (2). The crystal structure of d(CGCGAATICGCG) (3-9) has featured a sequence of ordered water molecules in the AATI region of the minor groove which has come to be known as the "spine of hydration" (6) and has been implicated in the preferential stability ofB-form DNA at high humidity (6,9). The base pairs in the crystallographic d(CGCGAATICGCG) exhibit a distinct propeller twist, which positions the hydrogen bond accepting atoms A-N3 and T-02 in the minor groove at ca. 3.7 A apart. The water molecules hydrating the nucleic acid atoms along the floor of the minor groove in the crystal structure are seen to be bridging these positions. The hydration of a canonical B-form of d(CGCGAATTCGCG) has recently been the subject of Monte Carlo simulations from this laboratory (10,11). Using proximity analysis and graphical presentations of hydration density, the nature of the hydration has been described. The calculations confirm the presence of an ordered water structure in the minor groove, but predict itto extend beyond the AATI region in the CGCG flanking sequences as well, thus extending throughout the minor groove of the B-form oligonucleotide. The major groove hydration features essentially saturation of hydrophilic sites and hydrophobic hydration around the T-CH3. The calculated backbone hydration consists of triads of water assembled into" cones of hydration" around the phosphates. The calculated patterns of hydration are generally consistent
1161
1162
Subramanian eta/.
with crystallographic and spectroscopic studies of nucleic acid hydration.
Downloaded by [Purdue University] at 14:08 17 January 2015
A specific discrepancy between the calculated hydration sites and the ordered water positions observed crystallographically was in the floor of the minor groove. Here the initial calculations (10,11) turned up monodentate hydrogen bonding to the acceptor atoms in the plane of the base pairs as opposed to A-N3 ...W...T-02 water bridges. There are two possible origins of this problem. One is in the choice of the canonical B form of DNA as a basis for the simulation studies. The second is the prescription chosen for the calculation of the intermolecular interaction energies, involving AMBER 3.0 charges (12) on the DNA atoms and the TIP4P water model (13). Subsequent studies, described herein, have been initiated to clarify the situation. We first carried out a Monte Carlo simulation completely analogous to that reported earlier, but assuming the crystal structure of the native dodecamer (3,4) rather than the canonical B form for the dodecamer. The calculation involved a screened charge model for d(CGCGAATTCGCG) together with 1951 water molecules (an excess of two hydration shells) in a hexagonal prism central cell under periodic boundary conditions. The volume of the system was taken to be consistent with an environmental density of 1 gm/cm 3 and the temperature was assumed as 298°K. The nucleic acid/water energy functions were taken to be AMBER 3.0/TIP4P. The simulation was carried out for an equilibration period of3000Kconfigurations, and the analysis was based on a production segment of lOOOK configurations. The average energy and other diagnostics in the simulation was seen to be stable over this segment of the realization. The calculated hydration density for the minor groove of the dodecamer from this simulation is shown in Figure 1, depicted for presentation here as the linear superposition of points representing oxygen coordinates of the solvent waters from a series of individual configurations taken at equally spaced intervals along the production segment of the realization. The clustering of such points is indicative of the position and localization of calculated hydration sites. The results of this simulation, as in the previous simulation assuming the canonical B form, predict sequential, monodentate hydrogen bonding in the AATT region coincident with the planes of the base pairs and are frame-shifted from the observed ordered water positions (large spheres in Figure 1), and do not account for the A-N3 ...W...T-02 water bridges observed in the crystal structure. We subsequently configured a completely independent Monte Carlo simulation based on the native dodecamer structure and 2106 water molecules, with an environmental density ofl gm/cc and a temperature of298°K. The potential functions used to describe the intermolecular interactions were based on GROMOS parameters for the DNA ( 14) and the SPC model for water ( 15). This calculation was carried out on a molecular simulation program developed by Swaminathan ( 16) with extensive modification and additional vectorization from GROMOS (14). Fully anionic phosphates and 22 Na + counterions were included. Spherical cutoffs were applied to all potentials with a switching function feathering the interaction energy to zero between 7.5 and 8.5 A. The cut-offwas applied on a group-by-group basis. The size
Downloaded by [Purdue University] at 14:08 17 January 2015
Spine of Hydration in CGCGAATTCGCG
1163
Figure 1: Calculated first shell hydration density in the minor groove of the native crystallographic form of d(CGCGAATICGCG) based on AMBER 3.0 charges for nucleic acid atoms and hte TIP4P model for water, presented as a superposition ofwateroxygen positions from 19 snapshots of equally spaced intervals along the lSOOK Monte Carlo realization. Large oepn circles are the position of the crystallographic ordered water comprising the observed spine of hydration (6).
of the hexagonal prism unit was chosen so that all solute-solvent interactions die off within the central cell. The calculations were carried out on a CRAY YMP at the Pittsburgh Supercomputer Center at a much improved sampling rate of 2300K configurations/hr. and involve lO,OOOK equilibration steps and lO,OOOK configurations of production. The results of the GROMOS/SPC Monte Carlo simulation on the hydration density in the minor groove of the dodecamer are shown in Figure 2. The calculated localizations ofhydration density are seen to coincide almost perfectly with the four experimentally determined positions. In particular along the floor of the AATT region of the minor groove, the most populous region ofhydration density corresponds to the position of the best determined crystallographic water and the lowest temperature factor. The interface between the GC and AT tracts in the sequence features a paucity of hydration density, consistent with the ideas about disruption of the spine advanced by Dickerson and coworkers (9). There is however considerable localization of hydration density in the GC tracks, expanding into a double ribbon
Downloaded by [Purdue University] at 14:08 17 January 2015
1164
Subramanian et a/.
I
•,.
Figure 2: Calculated first shell hydration density in the minor groove of d(CGCGAATTCGCG) based on GROMOS charges for the nucleic acid and the SPC model for water, based on a superposition of 40 structures. See caption to Figure I for further details.
motif as the minor groove widens toward the ends. This is consistent with observations on GC hydration in a recent crystal structure on a related sequence by Prive et al. (17). In summary, we find on the basis of two additional Monte Carlo simulations on the hydration of d(CGCGAATTCGCG) that the discrepancy with experiment observed for the ordered water positions along the floor of the minor groove in the spine of hydration is apparently due not only to our choice of the canonical rather than crystallographic form as a reference, but either to the prescription chosen for the intermolecular potential functions or the indirect effects involving electrostatics of the phosphates. The former is the more likely explanation, since the direct hydrogen bonding interactions of water molecules with groove atoms are expected to be dominant over long range indirect effects. The results are seen to be sensitive to the description of configurational energy. The GROMOS 12-6-1 non-bonded parameters and SPC model for water are shown in a simulation of considerable length to give a nearly perfecttheoretical account of the observed crystallographic ordered water positions in the spine of hydration.
Spine of Hydration in CGCGAATTCGCG
1165
Good agreement between calculated and observed water structure in related systems a and ~-cyclodextrine [18) and dCpG/proflavine [19) has also been reported based on the G ROMOS/SPC prescription for intermolecular potentials. Establishing an accurate theoretical account of the observed hydration structure is an important step in the validation of molecular simulation applied to nucleic acid systems.
Downloaded by [Purdue University] at 14:08 17 January 2015
Acknowledgments This research was supported by grants to DLB from the National Institutes of Health (GM-37909) and the National Science Foundation (CHE-8696117), and the Office ofN aval Research (N -00014-87-K-0312). Support from the Bristol Myers Corporation via a Connecticut Cooperative High Technology Research and Development Grant is also gratefully acknowledged. Access to the CRAYYMP for processing these calculations was provided by the National Science Foundation and the Pittsburgh Supercomputer Center. References and Footnotes
l. W. Saenger, Principles of Nucleic Acid Structure, Springer Verlag, New York (1983). 2. For a recent review, see E. Westhof and D.L. Beveridge in "Water Science Reviews, Vol. Ill, F. Franks, ed., Cambridge University Press, in press. 3. R.M. Wing, H.R. Drew, T. Takano, C. Broka, S. Tanaka and R.E. Dickerson, Nature 278, 755 (1980). 4. H.R. Drew, R.M. Wing, T. Takano, C. Broka, S. Tanaka, K. Itakure and R.E. Dickerson, Proc. Nat/. Acad. Sci. USA 78,2179 (1981). 5. R.E. Dickerson and H.R. Drew,J Mol. Bioi. 149,761 (1981). 6. H.R. Drew and R.E. Dickerson,!. Mol. Bioi. 151,535 (1981). 7. H.R. Drew, S. Samson and R.E. Dickerson, Proc. Nat/. Acad. Sci. USA 79, 4040 ( 1982). 8. AV. Fantini, M.L. Kopka, H.R.Drew and R.E. Dickerson,!. Bioi. Chern. 257,14868 (1982). 9. M.L. Kopka, AV. Fratini, H.R. Drew and R.E. Dickerson, J. Mol. Bioi. 163, 129 (1983). 10. P.S. Subramanian, G. Ravishanker and D.L. Beveridge, Proc. Nat/. Acad. Sci. USA 85, 1836 (1988). 11. P.S. Subramanian and D.L. Beveridge,! Biomol. Str. Dyn. 6, 1093 (1989). 12. S.J. Weiner, P.A. Kollman, D. Case, U.C. Singh, C. Ghio, G. Alagona, S. Profata and P. Weiner,!. Am. Chern. Soc. 106, 765 (1984). 13. W.L. Jorgensen, J. Chandrasakar, J. Madura, R.W. Impey and M.L. Klein, J. Chern. Phys. 79, 926 (1983). 14. W.F. van Gunsteren and H.J.C. Berendsen, GROMOS: Groningen Molecular Simulation System, University ofGroningen (1988). 15. H.J.C. Berendsen, J.P.M. Postma, W.F. van Gunsteren and J. Harmons, in Intermolecular Forces, B. Pullman, ed., Reidel, Drodrect, The Netherlands, 331 (1981). 16. S. Swaminathan, WESMOS: Wesleyan Molecular Simulation System, Wesleyan University (1989). 17. R.E. Dickerson, inStructure&Methods, Vol.3: DNA& RNA, eds., R.H. Sarma and M.H. Sarma, 001038, Adenine Press, Guilderland, N.Y. (1990). 18. J.E.H. Koehler, W. Saenger and W.F. van Gunsteren, Eur. J. Biophys. 15, 197 (1987). 19. S. Swaminathan, D.L. Beveridge and H.M. Berman,! Phys. Chern., in press (1990). Date Received: September 18,1989
Communicated by the Editor R.H. Sarma
