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Systematic Validation of Protein Force Fields against Experimental Data

Open access
Lindorff-Larsen, Kresten, Maragakis, Paul, Piana, Stefano, Eastwood, Michael P., Dror, Ron O., Shaw, David E.·2012·PLoS ONE
DOI 10.1371/journal.pone.0032131
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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 α-helical, the other with β-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 properties of proteins.

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Metadata

Authors
Lindorff-Larsen, K., Maragakis, P., Piana, S., Eastwood, M. P., Dror, R. O., & Shaw, D. E.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-02-22
Volume
7
Issue
2
Pages
e32131
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0032131
OpenAlex
W2037159954
Cited by
645
References
3
FWCI
22.89
Type
journal article
Language
en
Update notices
correction (2013-04-26)
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: Systematic Validation of Protein Force Fields against Experimental Data. https://app.cochat.ai/papers/10.1371/journal.pone.0032131
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Lindorff-Larsen, K., Maragakis, P., Piana, S., Eastwood, M. P., Dror, R. O., & Shaw, D. E. (2012). Systematic Validation of Protein Force Fields against Experimental Data. PLoS ONE. https://doi.org/10.1371/journal.pone.0032131

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