基于量子化学的药物共晶虚拟筛选方法研究进展  

Advances in Virtual Pharmaceutical Cocrystals Screening Methods Based on Quantum Chemistry

作　　者：于铭超 王志鹏 杨世颖[1] 杨德智[1] 吕扬[1] YU Mingchao;WANG Zhipeng;YANG Shiying;YANG Dezhi;LYU Yang(Beijing Key Laboratory of Polymorphs Drugs Research,Peking Union Medical College,Institute of Materia Medical,Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]北京协和医学院、中国医学科学院药物研究所晶型药物研究北京市重点实验室,北京100050

出　　处：《医药导报》2022年第5期642-648,共7页Herald of Medicine

基　　金：国家科技重大专项-重大新药创制(2018ZX09711001-010)。

摘　　要：随着药物共结晶技术的发展,以筛选药物共晶配体为目的的快速高通量筛选方法引起了广大科研工作者的极大关注。在药物共晶配体的预测和快速筛选中常用的理论计算方法有:①基于分子表面静电势的虚拟共晶设计方法,通过计算分子表面静电势来确定分子表面可能的分子间相互作用位点,为分子间识别提供了可靠的指导原则。②依据Hansen溶解度参数的设计理论,通过计算药物活性成分与共晶配体的Hansen溶解度差来对形成共晶的可行性进行预测,实现对共晶配体的快速筛选。③依据液相热力学理论的COSMO-RS计算模型,使用由第一性原理计算得出的屏蔽电荷密度结合快速统计热力学来计算溶液中化合物的化学势,为快速筛选共晶配体提供了一种高效的方法。该文旨在通过比较3种常用共晶虚拟筛查方法的优缺点,为虚拟共晶筛选在药物共晶领域的进一步应用提供参考。With the development of pharmaceutical cocrystallization technology,rapid and high-throughput screening methods for screening pharmaceutical cocrystal formers have attracted great attention of researchers.This article summarizes the role of three commonly used cocrystal screening theoretical calculation methods in the prediction and rapid screening of pharmaceutical cocrystal formers,including:①The virtual cocrystal design method based on molecular surface electrostatic potential.The possible intermolecular interaction sites on the molecular surface are determined by calculating the molecular surface electrostatic potential,which provides a reliable guiding principle for intermolecular recognition.②According to the design theory of Hansen solubility parameters,the feasibility of cocrystal formation can be predicted by calculating the Hansen solubility difference between the active pharmaceutical ingredients and the cocrystal formers,so as to realize the rapid screening of cocrystal formers.③Based on the COSMO-RS calculation model of liquid phase thermodynamics theory,the chemical potential of compounds in solution is calculated by using the shielding charge density calculated by the first principle combined with rapid statistical thermodynamics,which provides an efficient method for rapid screening of cocrystal formers.This paper aims to provide reference for the further application of virtual cocrystal screening in the field of pharmaceutical cocrystallization by comparing the advantages and disadvantages of three common cocrystal virtual screening methods.

关 键 词：药物共晶 量子化学 虚拟筛选 理论计算 

分 类 号：R917[医药卫生—药物分析学]