Hassan Nafisa M, Alhossary Amr A, Mu Yuguang, Kwoh Chee-Keong
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Sci Rep. 2017 Nov 13;7(1):15451. doi: 10.1038/s41598-017-15571-7.
"Virtual Screening" is a common step of in silico drug design, where researchers screen a large library of small molecules (ligands) for interesting hits, in a process known as "Docking". However, docking is a computationally intensive and time-consuming process, usually restricted to small size binding sites (pockets) and small number of interacting residues. When the target site is not known (blind docking), researchers split the docking box into multiple boxes, or repeat the search several times using different seeds, and then merge the results manually. Otherwise, the search time becomes impractically long. In this research, we studied the relation between the search progression and Average Sum of Proximity relative Frequencies (ASoF) of searching threads, which is closely related to the search speed and accuracy. A new inter-process spatio-temporal integration method is employed in Quick Vina 2, resulting in a new docking tool, QuickVina-W, a suitable tool for "blind docking", (not limited in search space size or number of residues). QuickVina-W is faster than Quick Vina 2, yet better than AutoDock Vina. It should allow researchers to screen huge ligand libraries virtually, in practically short time and with high accuracy without the need to define a target pocket beforehand.
“虚拟筛选”是计算机辅助药物设计中的一个常见步骤，研究人员在这个过程中通过“对接”从一个小分子（配体）大库中筛选出感兴趣的命中物。然而，对接是一个计算量很大且耗时的过程，通常限于小尺寸的结合位点（口袋）和少量相互作用的残基。当目标位点未知时（盲对接），研究人员会将对接框分成多个框，或者使用不同的种子多次重复搜索，然后手动合并结果。否则，搜索时间会变得长得不切实际。在本研究中，我们研究了搜索进程与搜索线程的平均接近频率总和（ASoF）之间的关系，这与搜索速度和准确性密切相关。Quick Vina 2采用了一种新的进程间时空整合方法，产生了一种新的对接工具QuickVina-W，这是一种适用于“盲对接”的工具（不受搜索空间大小或残基数量的限制）。QuickVina-W比Quick Vina 2更快，但比AutoDock Vina更好。它应该能让研究人员在几乎不需要预先定义目标口袋的情况下，在实际短时间内以高精度虚拟筛选巨大的配体库。
