A point‐charge force field for molecular mechanics simulations of proteins based on condensed‐phase quantum mechanical calculations

Journal of Computational Chemistry - Tập 24 Số 16 - Trang 1999-2012 - 2003
Yong Duan1, Chun Wu2, Shibasish Chowdhury2, Mathew C. Lee2, Guoming Xiong2, Wei Zhang2, Rong Yang2, Piotr Cieplak3,4, Ray Luo4, Lee T3,4, James W. Caldwell4, Junmei Wang5, Peter A. Kollman4
1Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716 USA
2University of Delaware
3Accelrys Inc.
4University of California at San Francisco
5The Green Center for Systems Biology

Tóm tắt

AbstractMolecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third‐generation point‐charge all‐atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc‐pVTZ//HF/6‐31G** quantum mechanical methods. The main‐chain torsion parameters were obtained by fitting to the energy profiles of Ace‐Ala‐Nme and Ace‐Gly‐Nme di‐peptides calculated using MP2/cc‐pVTZ//HF/6‐31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of ε = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed‐phase simulations of proteins. Initial tests on peptides demonstrated a high‐degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace‐Gly‐Nme and Ace‐Ala‐Nme di‐peptides. Some highlights of our results include (1) well‐preserved balance between the extended and helical region distributions, and (2) favorable type‐II poly‐proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornell et al. charge sets, as judged by overall agreement between dipole moments, allows a smooth transition to the new force field in the area of ligand‐binding calculations. Test simulations on a large set of proteins are also discussed. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1999–2012, 2003

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Tài liệu tham khảo

10.1063/1.470117

10.1073/pnas.92.8.3190

10.1021/ja9727023

10.1126/science.282.5389.740

10.1023/A:1007907925007

10.1146/annurev.physchem.51.1.129

10.1021/ja9939385

10.1021/ja0273851

10.1038/nature01160

10.1021/ja028604l

10.1016/S0022-2836(03)00177-3

10.1016/S0959-440X(97)80005-X

10.1073/pnas.95.4.1562

10.1073/pnas.95.17.9897

Voter A. F., 1998, Phys Rev B, 57, 985, 10.1103/PhysRevB.57.R13985

10.1006/jmbi.2001.5033

10.1002/jcc.540070216

10.1126/science.3576184

10.1021/ja00124a002

10.1006/jmbi.1996.0330

10.1006/jmbi.1997.1247

Cieplak P.;Caldwell J.;Kollman P. A. personal communication.

10.1002/jcc.10125

10.1002/jcc.1079

10.1021/j100142a004

Frisch M. J., 2001, Gaussian 98

10.1103/PhysRevB.37.785

10.1063/1.464913

10.1016/0009-2614(89)87234-3

10.1063/1.462569

10.1016/S0166-1280(98)00553-3

10.1007/s002140000239

10.1063/1.474659

Kollman P. A., 1997, Computer Simulations of Biological Systems

10.1063/1.445869

Berendsen H. J. C., 1984, J Comp Phys, 81, 3684

Wang G., 2003, Bioinformatics, 9, 1589, 10.1093/bioinformatics/btg224

10.1021/jp003919d

10.1021/ja962310g

10.1039/P29930000799

10.1021/j100007a062

10.1063/1.469990

10.1063/1.472829

10.1002/prot.10279

10.1002/prot.10286

10.1021/bi9706677

10.1073/pnas.112193999

10.1002/bip.10216

Lee M. C., 2003, Proteins

10.1021/jp994157t

10.1002/(SICI)1097-0134(199705)28:1<59::AID-PROT6>3.0.CO;2-E

10.1021/jp027293y

10.1002/(SICI)1097-0134(199606)25:2<202::AID-PROT6>3.0.CO;2-J

10.1110/ps.0240103

10.1002/prot.10171

10.1002/jcc.10018

10.1021/ja9621760

10.1016/S0301-4622(96)02238-7

10.1016/S0006-3495(00)76411-3

10.1021/j100665a011

10.1006/jmbi.1996.0256

10.1073/pnas.181328398

10.1002/prot.1087

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Journal of Computational Chemistry

Tập 24 Số 16

1999-2012

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