Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field Export

@article{citeulike:3171690, abstract = {Biological function of biomolecules is accompanied by a wide range of motional behavior. Accurate modeling of dynamics by molecular dynamics (MD) computer simulations is therefore a useful approach toward the understanding of biomolecular function. NMR spin relaxation measurements provide rigorous benchmarks for assessing important aspects of MD simulations, such as the amount and time scales of conformational space sampling, which are intimately related to the underlying molecular mechanics force field. Until recently, most simulations produced trajectories that exhibited too much dynamics particularly in flexible loop regions. Recent modifications made to the backbone and psi torsion angle potentials of the AMBER and CHARMM force fields indicate that these changes produce more realistic molecular dynamics behavior. To assess the consequences of these changes, we performed a series of 520 ns molecular dynamics trajectories of human ubiquitin using the AMBER99 and AMBER99SB force fields for different conditions and water models and compare the results with NMR experimental backbone NH S2 order parameters. A quantitative analysis of the trajectories shows significantly improved agreement with experimental NMR data for the AMBER99SB 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 is found that comparison of experimental and back-calculated NMR spin-relaxation data provides a more objective way of assessing the quality of the trajectory than order parameters alone. Analysis of a key mobile beta-hairpin in ubiquitin demonstrates that the dynamics of mobile sites are not only reduced by the modified force field, but the extent of motional correlations between amino acids is also markedly diminished.}, address = {Department of Chemistry and Biochemistry and National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32306}, author = {Showalter, Scott A. and Bruschweiler, Rafael}, citeulike-article-id = {3171690}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ct7000045}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ct7000045}, day = {1}, doi = {10.1021/ct7000045}, journal = {Journal of Chemical Theory and Computation}, keywords = {folding, forcefield}, month = {May}, number = {3}, pages = {961--975}, posted-at = {2009-06-16 11:34:29}, priority = {2}, title = {Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field}, url = {http://dx.doi.org/10.1021/ct7000045}, volume = {3}, year = {2007} }

TY - JOUR ID - citeulike:3171690 L3 - citeulike-article-id:3171690 N2 - Biological function of biomolecules is accompanied by a wide range of motional behavior. Accurate modeling of dynamics by molecular dynamics (MD) computer simulations is therefore a useful approach toward the understanding of biomolecular function. NMR spin relaxation measurements provide rigorous benchmarks for assessing important aspects of MD simulations, such as the amount and time scales of conformational space sampling, which are intimately related to the underlying molecular mechanics force field. Until recently, most simulations produced trajectories that exhibited too much dynamics particularly in flexible loop regions. Recent modifications made to the backbone and psi torsion angle potentials of the AMBER and CHARMM force fields indicate that these changes produce more realistic molecular dynamics behavior. To assess the consequences of these changes, we performed a series of 520 ns molecular dynamics trajectories of human ubiquitin using the AMBER99 and AMBER99SB force fields for different conditions and water models and compare the results with NMR experimental backbone NH S2 order parameters. A quantitative analysis of the trajectories shows significantly improved agreement with experimental NMR data for the AMBER99SB 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 is found that comparison of experimental and back-calculated NMR spin-relaxation data provides a more objective way of assessing the quality of the trajectory than order parameters alone. Analysis of a key mobile beta-hairpin in ubiquitin demonstrates that the dynamics of mobile sites are not only reduced by the modified force field, but the extent of motional correlations between amino acids is also markedly diminished. IS - 3 JF - Journal of Chemical Theory and Computation AD - Department of Chemistry and Biochemistry and National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32306 EP - 975 TI - Validation of Molecular Dynamics Simulations of Biomolecules Using NMR Spin Relaxation as Benchmarks: Application to the AMBER99SB Force Field VL - 3 SP - 961 KW - folding KW - forcefield AU - Showalter, Scott AU - Bruschweiler, Rafael PY - 2007/05/01/ UR - http://dx.doi.org/10.1021/ct7000045 ER -