Booth Jonathan J, Shalashilin Dmitrii V
School of Chemistry, University of Leeds , Leeds LS2 9JT, U.K.
J Phys Chem B. 2016 Feb 4;120(4):700-8. doi: 10.1021/acs.jpcb.5b11519. Epub 2016 Jan 25.
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.
报道了通过原子力显微镜（AFM）在力钳（FC）和速度钳（VC）模式下对蛋白质展开进行盒装动力学（BXD）全原子模拟的结果。在AFM实验中，展开发生的时间尺度对于标准的原子分子动力学（MD）模拟来说太长了，标准的MD模拟通常会添加比实验力大许多数量级的力。BXD可以达到缓慢展开的时间尺度，并对非常高自由能的展开途径进行采样，再现拉力与伸长以及伸长与时间的实验依赖性。计算结果显示了先前在VC AFM实验中观察到的拉力“峰值”的存在，并能够识别导致这些峰值的中间蛋白质构象。全原子BXD模拟可以估计FC实验中长达秒级时间尺度的展开速率。
