分子对接软件在药物设计中的应用  

Application of molecule docking software in drug design

作　　者：赵晨[1] 夏春光 于敏 潘月[1] 王辂[1] 

机构地区：[1]成都大学四川抗菌素工业研究所,成都610052 [2]正大天晴药业集团股份有限公司,连云港222062

出　　处：《中国抗生素杂志》2015年第3期234-240,共7页Chinese Journal of Antibiotics

基　　金：四川省科技厅杰出青年基金项目(No.2013JQ0050);成都大学校青年基金项目(No.2014XQCKS08)

摘　　要：近10年来,随着X-射线晶体学和高通量测序等技术的不断发展,越来越多的蛋白晶体结构得到确证,其相应的基因信息也随之公布。蛋白质等生物大分子结构和功能信息的"井喷",产生了愈来愈多的药物靶标,加之计算科学的蓬勃发展亦极大地促进了分子对接和虚拟筛选技术在药物设计领域的应用推广。如今,计算技术已成为药物设计领域的重要手段之一,通过计算机模拟的分子对接运算,研究人员能快速准确地描述药物与靶标间的相互作用,从而缩短了药物研发周期。本文简要介绍了分子对接化学机理、分子表征方法以及3种分子对接机制。同时着重介绍了一些在药物设计中广泛使用的分子对接软件,包括Auto Dock、SLIDE、DOCK以及Auto Dock Vina。这些软件分别采用不同的搜索算法以及打分函数,但其功能较为相似且囊括了分子对接领域的最近研究进展。为了使分子对接过程更为方便快捷,研究者们不断更新计算技术,推出各种图形分析工具。最后,以G蛋白偶联受体和蛋白激酶为例,简要说明分子对接及虚拟筛选领域的部分研究成果。Over the past ten years, with scientific and technology advances such as X-ray crystallography and high-throughout sequencing, three-dimensional structures of protein are identified increasingly than ever before, and the gene information becomes available as well. Progress in structural and functional studies on biological macromolecules is generating more and more potential pharmaceutical targets for drug development. The great developments of computing science become the driving forces which lead to the application of molecule docking and virtual screening in drug design. Nowadays, computing technology becomes one of the most important approaches in drug research and development. Through docking simulation programs, researchers characterize the molecular conformations of most substrates or ligands with their biological targets with high accuracy and efficiency, and it is beneficial for better understanding of drug-target interactions. It speed up drug discovery and shorten times to market. In this review, molecule docking theories are briefly introduced, including chemical mechanism, molecular representation methods and docking mechanism （rigid body docking or flexible docking）. At the same time, some molecule docking programs which are widely used in the context of drug design are discussed here in detail, including AutoDoek （by The Scripps Research Institute）, SLIDE （by Michigan State University）, DOCK （by University of California San Francisco） and AutoDock Vina （by The Scripps Research Institute）. The programs offer distinct searching methods and scoring functions which are actually with similar functions, however, the recent improvements of these programs do reflect the latest progress in docking field. Researchers exert themselves to improve computing science and technology, therefore, several visualization and analysis tools for molecule docking program are released and updated so that docking process is more convenient and speedy. In the end of this review, there are two exemplar cas

关 键 词：药物设计 分子对接 虚拟筛选 蛋白质 

分 类 号：R97[医药卫生—药品]