Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field
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- 作者：Scott A. Showalter ; Rafael Brü ; schweiler
- 刊名：Journal of Chemical Theory and Computation
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：3
- 期：3
- 页码：961 - 975
- 全文大小：375K
- 年卷期：v.3,no.3(May 2007)
- ISSN：1549-9626
文摘
Biological function of biomolecules is accompanied by a wide range of motionalbehavior. Accurate modeling of dynamics by molecular dynamics (MD) computer simulations istherefore a useful approach toward the understanding of biomolecular function. NMR spinrelaxation measurements provide rigorous benchmarks for assessing important aspects of MDsimulations, such as the amount and time scales of conformational space sampling, which areintimately related to the underlying molecular mechanics force field. Until recently, mostsimulations produced trajectories that exhibited too much dynamics particularly in flexible loopregions. Recent modifications made to the backbone 
and 
torsion angle potentials of theAMBER and CHARMM force fields indicate that these changes produce more realistic moleculardynamics behavior. To assess the consequences of these changes, we performed a series of5-20 ns molecular dynamics trajectories of human ubiquitin using the AMBER99 andAMBER99SB force fields for different conditions and water models and compare the resultswith NMR experimental backbone N-H S2 order parameters. A quantitative analysis of thetrajectories shows significantly improved agreement with experimental NMR data for theAMBER99SB force field as compared to AMBER99. Because NMR spin relaxation data (T1,T2, NOE) reflect the combined effects of spatial and temporal fluctuations of bond vectors, it isfound that comparison of experimental and back-calculated NMR spin-relaxation data providesa more objective way of assessing the quality of the trajectory than order parameters alone.Analysis of a key mobile 
-hairpin in ubiquitin demonstrates that the dynamics of mobile sitesare not only reduced by the modified force field, but the extent of motional correlations betweenamino acids is also markedly diminished.
and torsion angle potentials of theAMBER and CHARMM force fields indicate that these changes produce more realistic moleculardynamics behavior. To assess the consequences of these changes, we performed a series of5-20 ns molecular dynamics trajectories of human ubiquitin using the AMBER99 andAMBER99SB force fields for different conditions and water models and compare the resultswith NMR experimental backbone N-H S2 order parameters. A quantitative analysis of thetrajectories shows significantly improved agreement with experimental NMR data for theAMBER99SB force field as compared to AMBER99. Because NMR spin relaxation data (T1,T2, NOE) reflect the combined effects of spatial and temporal fluctuations of bond vectors, it isfound that comparison of experimental and back-calculated NMR spin-relaxation data providesa more objective way of assessing the quality of the trajectory than order parameters alone.Analysis of a key mobile -hairpin in ubiquitin demonstrates that the dynamics of mobile sitesare not only reduced by the modified force field, but the extent of motional correlations betweenamino acids is also markedly diminished.