Equilibrium sampling for biomolecules under mechanical tension.

Abstract:

:In the studies of force-induced conformational transitions of biomolecules, the large timescale difference from experiments presents the challenge of obtaining convergent sampling for molecular dynamics simulations. To circumvent this fundamental problem, an approach combining the replica-exchange method and umbrella sampling (REM-US) was developed to simulate mechanical stretching of biomolecules under equilibrium conditions. Equilibrium properties of conformational transitions can be obtained directly from simulations without further assumptions. To test the performance, we carried out REM-US simulations of atomic force microscope (AFM) stretching and relaxing measurements on the polysaccharide pustulan, a (1-->6)-beta-D-glucan, which undergoes well-characterized rotameric transitions in the backbone bonds. With significantly enhanced sampling convergence and efficiency, the REM-US approach closely reproduced the equilibrium force-extension curves measured in AFM experiments. Consistent with the reversibility in the AFM measurements, the new approach generated identical force-extension curves in both stretching and relaxing simulations-an outcome not reported in previous studies, proving that equilibrium conditions were achieved in the simulations. REM-US may provide a robust approach to modeling of mechanical stretching on polysaccharides and even nucleic acids.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Zeng X,Hu H,Zhou HX,Marszalek PE,Yang W

doi

10.1016/j.bpj.2009.11.004

subject

Has Abstract

pub_date

2010-02-17 00:00:00

pages

733-40

issue

4

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)01727-5

journal_volume

98

pub_type

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