Li Lin, Alper Joshua, Alexov Emil
Department of Physics, Clemson University, Clemson, SC 29634, USA.
Sci Rep. 2016 Mar 18;6:23249. doi: 10.1038/srep23249.
Many biological phenomena involve the binding of proteins to a large object. Because the electrostatic forces that guide binding act over large distances, truncating the size of the system to facilitate computational modeling frequently yields inaccurate results. Our multiscale approach implements a computational focusing method that permits computation of large systems without truncating the electrostatic potential and achieves the high resolution required for modeling macromolecular interactions, all while keeping the computational time reasonable. We tested our approach on the motility of various kinesin motor domains. We found that electrostatics help guide kinesins as they walk: N-kinesins towards the plus-end, and C-kinesins towards the minus-end of microtubules. Our methodology enables computation in similar, large systems including protein binding to DNA, viruses, and membranes.
许多生物学现象涉及蛋白质与大的物体的结合。由于引导结合的静电力作用距离较远，为便于计算建模而截断系统大小常常会产生不准确的结果。我们的多尺度方法实施了一种计算聚焦方法，该方法允许在不截断静电势的情况下对大型系统进行计算，并实现建模大分子相互作用所需的高分辨率，同时保持计算时间合理。我们在各种驱动蛋白运动结构域的运动性上测试了我们的方法。我们发现，静电作用有助于引导驱动蛋白移动：N端驱动蛋白朝向微管的正端移动，C端驱动蛋白朝向微管的负端移动。我们的方法能够在类似的大型系统中进行计算，包括蛋白质与DNA、病毒和膜的结合。
