[{"data":1,"prerenderedAt":214},["ShallowReactive",2],{"content-query-Px8YmxiKJr":3},{"_path":4,"_dir":5,"_draft":6,"_partial":6,"_locale":7,"title":8,"description":9,"date":10,"cover":11,"type":12,"category":13,"body":14,"_type":208,"_id":209,"_source":210,"_file":211,"_stem":212,"_extension":213},"/technology-blogs/zh/1419","zh",false,"","MindSpore 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、溶剂化效应等因素。",{"type":18,"tag":26,"props":145,"children":146},{},[147],{"type":24,"value":148},"分子对接技术被广泛应用于计算机辅助药物设计(Computer-Aided Drug Design, CADD)中。CADD为对药物分子的结构-活性关系、疾病的生物靶标分子的性质等进行计算、分析和预测，从而指导新型药物的发现。",{"type":18,"tag":26,"props":150,"children":151},{},[152],{"type":18,"tag":58,"props":153,"children":156},{"alt":154,"src":155},"6.jpg","https://bbs-img.huaweicloud.com/data/forums/attachment/forum/20224/13/1649835859933700638.jpg",[],{"type":18,"tag":26,"props":158,"children":159},{},[160],{"type":24,"value":161},"图1 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虚拟筛选流程",{"type":18,"tag":26,"props":181,"children":182},{},[183],{"type":24,"value":184},"介绍了两者的基础知识，再来说一说两者的优缺点。分子对接在对接时的条件比较简单，只需要对小分子和蛋白质进行预处理，之后就可以使用处理后的文件来进行对接，打分。而且对接的速度比较快，几天时间就可以迅速获取几万个小分子与蛋白质结合后的复合物的得分，从而筛选出有高亲和性的小分子。",{"type":18,"tag":26,"props":186,"children":187},{},[188],{"type":24,"value":189},"但是分子对接也有很多缺陷，在对接时，必须确定蛋白质的对接口袋，在预处理时把小分子放进这个口袋中，才能去实现对接过程，另外，在预处理时，水分子一直是一个难以处理的问题，因为人们很难确定在结合位点处哪些水分子是必须的，而哪些是可以去掉的，当然，在必要时，可以使用分子动力学模拟来解决该问题。另外，分子对接最关键的问题其实是它的准确率不高，打分不准，筛选出来的小分子的假阳性较高。",{"type":18,"tag":26,"props":191,"children":192},{},[193],{"type":24,"value":194},"分子动力学与分子对接不同，它的模拟结果更加准确，蛋白质与小分子对接所获得的构象与现实复合物的误差更小。而且分子动力学的应用更加广泛，既能研究配体结合的过程，还可以研究解除配体的过程。不过对应的，高精度的结果要求的也是更加苛刻的条件，需要确定的参数量以及溶剂环境的选择都会对结果产生非常大的影响。",{"type":18,"tag":26,"props":196,"children":197},{},[198],{"type":24,"value":199},"那么，如果使用分子对接和分子动力学分别进行虚拟筛选来获取对接构象，它们之间的区别是什么呢？对于分子对接，获取构象的方法一般是蒙特卡洛树搜索，是基于当前构象对配体施加随机平移旋转，从而获得新的构象，这多个构象为离散的构象，且任意两者之间没有直接的联系。而分子动力学则不同，通过模拟小分子的运动**，获得小分子与蛋白质对接直到稳定的整个过程，期间获取的所有构象均为在一个连续的变化中的某一个瞬间所获得的。所以构象与构象之间也会满足方程的关系。",{"type":18,"tag":26,"props":201,"children":202},{},[203],{"type":24,"value":204},"不过，无论是使用分子动力学还是分子对接，在CADD之后临床试验是一个必须的环节。而分子模拟只是在减少搜索小分子来进行人工实验的范围，减弱了传统的盲目筛选过程。",{"title":7,"searchDepth":206,"depth":206,"links":207},4,[],"markdown","content:technology-blogs:zh:1419.md","content","technology-blogs/zh/1419.md","technology-blogs/zh/1419","md",1776506112331]