Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan, ROC.
In Vivo. 2011 Mar-Apr;25(2):219-28.
HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear potential 1 (PLP1), piecewise linear potential 2 (PLP2), and potential of mean force (PMF) score of novel compounds. In this way, novel compounds with "de novo evolution" can be found. Using the the pharmacophore features that are near the receptor pocket and the score functions to calculate scores for the ligand-receptor interaction, the new ligands were selected, developed and virtually placed in the binding site of the receptor. A new compound, EVO12, gave the best score, indicating that it may be an efficient polymerase inhibitor of HCV NS5B.
HCV（丙型肝炎病毒）可导致慢性肝病。丙型肝炎病毒 NS5B RNA 依赖性 RNA 聚合酶（RbRp）和 NS3 蛋白酶能够影响基因的虚拟复制。计算机辅助药物设计（CADD）旨在设计具有药理活性的新分子。在这项研究中，我们使用 Discovery Studio 2.0 程序和评分函数来估计对接得分、分段线性势 1（PLP1）、分段线性势 2（PLP2）和平均力势（PMF）评分新型化合物。通过这种方式，可以找到具有“从头进化”的新型化合物。使用接近受体口袋的药效特征和评分函数来计算配体-受体相互作用的分数，选择、开发和虚拟放置新的配体在受体的结合位点上。新化合物 EVO12 的得分最高，表明它可能是一种有效的丙型肝炎病毒 NS5B 聚合酶抑制剂。
