论文标题
快速蛋白质折叠受内存依赖性摩擦的控制
Fast protein folding is governed by memory-dependent friction
论文作者
论文摘要
当通过低维反应坐标描述时，蛋白质折叠的速率由自由能屏障和摩擦之间的微妙相互作用确定。虽然从分子轨迹中提取自由化曲线是司空见惯的，但直接评估摩擦的评估更加难以捉摸，并且通常通过无内存反应速率理论间接评估它。在这里，使用基于广义Langevin方程（GLE）形式主义建立的内存内核提取方法，我们直接计算了八种快速折叠蛋白的内存依赖性摩擦，从一组已发表的大规模分子动力学蛋白模拟中获取。我们的结果表明，与共同的期望相反，在确定蛋白质折叠率时，尤其是对于较大的蛋白质，摩擦比自由能壁垒更重要。我们还表明，与基于无内存摩擦的预测相比，在某些情况下，有限摩擦的衰减时间可显着减少折叠时间的折叠时间。
When described by a low-dimensional reaction coordinate, the rates of protein folding are determined by a subtle interplay between free-energy barriers and friction. While it is commonplace to extract free-energy profiles from molecular trajectories, a direct evaluation of friction is far more elusive, and one typically evaluates it indirectly via memoryless reaction rate theories. Here, using memory-kernel extraction methods founded on a generalised Langevin equation (GLE) formalism, we directly calculate the memory-dependent friction for eight fast-folding proteins, taken from a published set of large-scale molecular dynamics protein simulations. Our results reveal that, contrary to common expectation, friction is more important than free energy barriers in determining protein folding rates, particularly for larger proteins. We also show that proteins fold in a regime where the finite decay time of friction significantly reduces the folding times, in some instances by as much as a factor of 10, compared to predictions based on memoryless friction.
