基于计算机虚拟筛选技术寻找NDM-1抑制剂  

Search for NDM-1 Inhibitors Based on Computer Virtual Screening Techniques

作　　者：冯迪 刘湲 孙影[1] 郑珩[1] 

机构地区：[1]中国药科大学生命科学与技术学院,南京210009

出　　处：《国外医药（抗生素分册）》2018年第2期111-115,共5页World Notes on Antibiotics

摘　　要：β-内酰胺类抗生素的广泛使用,使得越来越多的细菌产生由β-内酰胺酶介导的耐药性,针对丝氨酸β-内酰胺酶,目前已有克拉维酸、舒巴坦等抑制剂与临床常用抗生素配伍使用,但尚无金属β-内酰胺酶的有效抑制剂,因此,寻找金属β-内酰胺酶尤其是目前最受瞩目的新德里金属β-内酰胺酶-1[NDM-1(B1类)]的抑制剂是遏制"超级细菌"引起的感染最迫切的要求。虚拟筛选作为发现新的先导化合物、寻找新药物的有力手段,大大缩小了人工进行配体活性筛选研究范围。我们通过计算机虚拟筛选技术,利用Discovery Studio 2.5和GOLD 3.0平台,基于NDM-1晶体结构(PDB:3Q6X),从一个含有2059个天然产物分子的化合物库里筛选得到6个可能具有金属β-内酰胺酶NDM-1(B1类)抑制活性的化合物结构。The wide use of ^-lactam antibiotics makes more and more bacteria produce ^-lactamase- mediated resistance. For serine β-1actamase, inhibitors like clavulanic acid, Sulbactam are used in clinical treatment, which are combined with commonly used antibiotics. But there is no effective inhibitor of metal β-lactamase. Therefore, the inhibitors searched for metal β-1actamase, especially the most watched NDM- 1 （B1 class） are the most pressing requirements to contain infections caused by ＇super bacteria＇ As a powerful tool to find new lead compounds and new drugs, the virtual screening greatly reduces the scope for artificial screening of ligand activity. We screened from a library of 2059 natural product molecules based on the NDM- 1 crystal structure （PDB： 3Q6X） using computer-aided virtual screening via the Discovery Studio 2.5 and GOLD 3.0 platforms and get 6 compound structure which may have NDM-1 （class B1） inhibiting activity.

关 键 词：NDM-1酶 抑制剂 计算机虚拟筛选 

分 类 号：R978.1[医药卫生—药品]