Tunable, mixed-resolution modeling using library-based Monte Carlo and graphics processing units.
Tunable, mixed-resolution modeling using library-based Monte Carlo and graphics processing units.
复制标题
使用基于库的蒙特卡罗和图形处理单元进行可调的混合分辨率建模。
DOI：
10.1021/ct300263z
复制
发表时间：
2012
影响因子：
5.5
通讯作者：
Zuckerman,DanielM
中科院分区：
文献类型：
--
作者：
Mamonov,ArtemB;Lettieri,Steven;Ding,Ying;Sarver,JessicaL;Palli,Rohith;Cunningham,TimothyF;Saxena,Sunil;Zuckerman,DanielM
我们最近推出的基于库的蒙特卡罗（LBMC）方法的基础上，我们描述了一个灵活的协议，混合粗粒度（CG）/全原子（AA）模拟蛋白质和配体。在LBMC的本实施方案中，蛋白质侧链构型被预先计算并存储在文库中，而沿着主链的键合相互作用沿着被明确地处理。由于AA侧链坐标以最小的运行时成本维护，因此可以打开任意位点和相互作用项以创建混合分辨率模型。例如，感兴趣的AA区域如结合位点可以偶联至蛋白质其余部分的CG模型。我们还开发了适用于混合分辨率模型的广义Born/表面积（GBSA）隐式溶剂模型的混合实现，该模型又被移植到图形处理单元（GPU）以实现更快的计算。应用该软件研究了两个系统：（i）蛋白G（GB 1）B1结构域上自旋标记的行为;（ii）随机初始化雌二醇构型与雌激素受体（ERα）配体结合结构域的对接。GPU版本代码的性能也在许多其他系统中进行了基准测试。
Building on our recently introduced library-based Monte Carlo (LBMC) approach, we describe a flexible protocol for mixed coarse-grained (CG)/all-atom (AA) simulation of proteins and ligands. In the present implementation of LBMC, protein side chain configurations are precalculated and stored in libraries, while bonded interactions along the backbone are treated explicitly. Because the AA side chain coordinates are maintained at minimal run-time cost, arbitrary sites and interaction terms can be turned on to create mixed-resolution models. For example, an AA region of interest such as a binding site can be coupled to a CG model for the rest of the protein. We have additionally developed a hybrid implementation of the generalized Born/surface area (GBSA) implicit solvent model suitable for mixed-resolution models, which in turn was ported to a graphics processing unit (GPU) for faster calculation. The new software was applied to study two systems: (i) the behavior of spin labels on the B1 domain of protein G (GB1) and (ii) docking of randomly initialized estradiol configurations to the ligand binding domain of the estrogen receptor (ERα). The performance of the GPU version of the code was also benchmarked in a number of additional systems.