How Accurately Do Current Force Fields Predict Experimental Peptide Conformations? An Adiabatic Free Energy Dynamics Study

The quality of classical biomolecular simulations is inevitably limited by two problems: the accuracy of the force field used and the comprehensiveness of configuration space sampling. In this work we tackle the sampling problem by carrying out driven adiabatic free energy dynamics to obtain converg...

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Bibliographic Details
Published inThe journal of physical chemistry. B Vol. 118; no. 24; pp. 6539 - 6552
Main Authors Tzanov, Alexandar T, Cuendet, Michel A, Tuckerman, Mark E
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 19.06.2014
Subjects
Adiabatic flow
Algorithms
Dipeptides - chemistry
Dipeptides - metabolism
Dynamics
Free energy
Gas phases
Gases - chemistry
Mathematical analysis
Molecular Dynamics Simulation
Peptides
Populations
Protein Conformation
Sampling
Solutions - chemistry
Thermodynamics
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Summary:The quality of classical biomolecular simulations is inevitably limited by two problems: the accuracy of the force field used and the comprehensiveness of configuration space sampling. In this work we tackle the sampling problem by carrying out driven adiabatic free energy dynamics to obtain converged free energy surfaces of dipeptides in the gas phase and in solution using selected dihedral angles as collective variables. To calculate populations of conformational macrostates observed in experiment, we introduce a fuzzy clustering algorithm in collective-variable space, which delineates macrostates without prior definition of arbitrary boundaries. With this approach, we calculate the conformational preferences of small peptides with six biomolecular force fields chosen from among the most recent and widely used. We assess the accuracy of each force field against recently published Raman or IR–UV spectroscopy measurements of conformer populations for the dipeptides in solution or in the gas phase.
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ISSN:1520-6106
1520-5207
DOI:10.1021/jp500193w