systematic validation of protein force fields against experimental data针对实验数据的系统验证蛋白质的力场.pdf
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Systematic Validation of Protein Force Fields against
Experimental Data
1. 1. 1. 1 1
Kresten Lindorff-Larsen , Paul Maragakis , Stefano Piana , Michael P. Eastwood , Ron O. Dror ,
David E. Shaw1,2*
1 D. E. Shaw Research, New York, New York, United States of America, 2 Center for Computational Biology and Bioinformatics, Columbia University, New York, New York,
United States of America
Abstract
Molecular dynamics simulations provide a vehicle for capturing the structures, motions, and interactions of biological
macromolecules in full atomic detail. The accuracy of such simulations, however, is critically dependent on the force field—
the mathematical model used to approximate the atomic-level forces acting on the simulated molecular system. Here we
present a systematic and extensive evaluation of eight different protein force fields based on comparisons of experimental
data with molecular dynamics simulations that reach a previously inaccessible timescale. First, through extensive
comparisons with experimental NMR data, we examined the force fields’ abilities to describe the structure and fluctuations
of folded proteins. Second, we quantified potential biases towards different secondary structure types by comparing
experimental and simulation data for small peptides that preferentially populate either helical or sheet-like structures. Third,
we tested the force fields’ abilities to fold two small proteins—one a-helical, the other with b-sheet structure. The results
suggest that force fields have improved over time, and that the most recent versions, while not perfect, provide an accurate
description of many structural and dynamical prope
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