Deciphering the Shared and Specific Drug Resistance Mechanisms of Anaplastic Lymphoma Kinase via Binding Free Energy Computation
作者机构：Department of Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009JiangsuP.R.China Innovation Institute for Artificial Intelligence in Medicine of Zhejiang UniversityCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058ZhejiangP.R.China
出 版 物：《Research》 (研究（英文）)
年 卷 期：2024年第2023卷第1期
页 面：663-674页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0703[理学-化学] 100214[医学-肿瘤学] 10[医学]
基 金：the National Key R&D Program of China(2021YFE0206400) the National Natural Science Foundation of China(81603031) the Natural Science Foundation of Zhejiang Province(LQ21H300007) the Young Elite Scientists Sponsorship Program by CPU(131810011 and 1132010013)
主 题：drugs Anaplastic clinical
摘 要：Anaplastic lymphoma kinase(ALK),a tyrosine receptor kinase,has been proven to be associated with the occurrence of numerous *** there have been already at least 3 generations of ALK inhibitors approved by FDA or in clinical trials,the occurrence of various mutations seriously attenuates the effectiveness of the ***,most of the drug resistance mechanisms still remain ***,it is necessary to reveal the bottom reasons of the drug resistance mechanisms caused by the *** this work,on the basis of verifying the accuracy of 2 main kinds of binding free energy calculation methodologies[end-point method of Molecular Mechanics with Poisson-Boltzmann/Generalized Born and Surface Area(MM/PB(GB)SA)and alchemical method of Thermodynamic Integration(TI)],we performed a systematic analysis on the ALK systems to explore the underlying shared and specific drug resistance mechanisms,covering the one-drug-multiple-mutation and multiple-drug-onemutation cases.
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