Constant pH molecular dynamics in generalized born implicit solvent

被引:419
作者
Mongan, J
Case, DA
McCammon, JA
机构
[1] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[5] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[6] Howard Hughes Med Inst, La Jolla, CA 92093 USA
关键词
constant pH molecular dynamics; generalized Born; pKa prediction; Monte Carlo; lysozyme;
D O I
10.1002/jcc.20139
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A new method is proposed for constant pH molecular dynamics (MD), employing generalized Born (GB) electrostatics. Protonation states are modeled with different charge sets, and titrating residues sample a Boltzmann distribution of protonation states as the simulation progresses, using Monte Carlo sampling based on GB-derived energies. The method is applied to four different crystal structures of hen egg-white lysozyme (HEWL). pK(a) predictions derived from the simulations have root-mean-square (RMS) error of 0.82 relative to experimental values. Similarity of results between the four crystal structures shows the method to be independent of starting crystal structure; this is in contrast to most electrostatics-only models. A strong correlation between conformation and protonation state is noted and quantitatively analyzed, emphasizing the importance of sampling protonation states in conjunction with dynamics. (C) 2004 Wiley Periodicals, Inc.
引用
收藏
页码:2038 / 2048
页数:11
相关论文
共 39 条
[11]  
Case D.A., 2004, AMBER 8
[12]   INCORPORATING SOLVATION EFFECTS INTO DENSITY-FUNCTIONAL ELECTRONIC-STRUCTURE CALCULATIONS [J].
CHEN, JL ;
NOODLEMAN, L ;
CASE, DA ;
BASHFORD, D .
JOURNAL OF PHYSICAL CHEMISTRY, 1994, 98 (43) :11059-11068
[13]   Open source clustering software [J].
de Hoon, MJL ;
Imoto, S ;
Nolan, J ;
Miyano, S .
BIOINFORMATICS, 2004, 20 (09) :1453-1454
[14]   Improving the continuum dielectric approach to calculating pK(a)s of ionizable groups in proteins [J].
Demchuk, E ;
Wade, RC .
JOURNAL OF PHYSICAL CHEMISTRY, 1996, 100 (43) :17373-17387
[15]   Performance comparison of generalized born and Poisson methods in the calculation of electrostatic solvation energies for protein structures [J].
Feig, M ;
Onufriev, A ;
Lee, MS ;
Im, W ;
Case, DA ;
Brooks, CL .
JOURNAL OF COMPUTATIONAL CHEMISTRY, 2004, 25 (02) :265-284
[16]  
Frisch M.J., 2016, Gaussian 16 Revision C. 01. 2016, V01
[17]   Combining conformational flexibility and continuum electrostatics for calculating pKas in proteins [J].
Georgescu, RE ;
Alexov, EG ;
Gunner, MR .
BIOPHYSICAL JOURNAL, 2002, 83 (04) :1731-1748
[18]   ENERGETICS OF CHARGE CHARGE INTERACTIONS IN PROTEINS [J].
GILSON, MK ;
HONIG, BH .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1988, 3 (01) :32-52
[19]  
Hooft RWW, 1996, PROTEINS, V26, P363
[20]   VMD: Visual molecular dynamics [J].
Humphrey, W ;
Dalke, A ;
Schulten, K .
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 1996, 14 (01) :33-38