D. E. Shaw Research, 120 West 45th Street, New York, NY 10036, USA.
Science. 2010 Oct 15;330(6002):341-6. doi: 10.1126/science.1187409.
Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.
分子动力学（MD）模拟被广泛用于在原子细节水平上研究蛋白质的运动，但它们的时间尺度一直受到限制，无法达到许多生物学关键构象变化的时间尺度。我们通过在专用机器上进行极其长的全原子 MD 模拟，研究了蛋白质动力学中的两个基本过程——蛋白质折叠和折叠状态下的构象变化。对 WW 蛋白结构域的平衡模拟捕捉到了多个折叠和展开事件，这些事件始终遵循明确的折叠途径；对该蛋白组成亚结构的单独模拟揭示了该途径的可能决定因素。对折叠蛋白 BPTI 的 1 毫秒模拟揭示了少数结构上不同的构象状态，其可逆转换速度比这些状态内部的局部松弛速度慢 1000 多倍。
