Fully Atomistic Simulations of Protein Unfolding in Low Speed Atomic Force Microscope and Force Clamp Experiments with the Help of Boxed Molecular Dynamics

被引:12
作者
Booth, Jonathan J. [1 ]
Shalashilin, Dmitrii V. [1 ]
机构
[1] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England
基金
英国工程与自然科学研究理事会;
关键词
UNIMOLECULAR REACTION-RATES; MALTOSE-BINDING PROTEIN; ENERGY LANDSCAPE; MONTE-CARLO; IMMUNOGLOBULIN DOMAINS; MECHANICAL STABILITY; INFREQUENT EVENTS; DIFFUSION-THEORY; TIME SCALES; TITIN;
D O I
10.1021/acs.jpcb.5b11519
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The results of boxed dynamics (BXD) fully atomistic simulations of protein unfolding by atomic force microscopy (AFM) in both force clamp (FC) and velocity clamp (VC) modes are reported. In AFM experiments the unfolding occurs on a time scale which is too long for standard atomistic molecular dynamics (MD) simulations, which are usually performed with the addition of forces which exceed those of experiment by many orders of magnitude. BXD can reach the time scale of slow unfolding and sample the very high free energy unfolding pathway, reproducing the experimental dependence of pulling force against extension and extension against time. Calculations show the presence of the pulling force "humps" previously observed in the VC AFM experiments and allow the identification of intermediate protein conformations responsible for them. Fully atomistic BXD simulations can estimate the rate of unfolding in the FC experiments up to the time scale of seconds.
引用
收藏
页码:700 / 708
页数:9
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