Helgren Travis R, Hagen Timothy J
Department of Chemistry and Biochemistry, Northern Illinois University, 1425 West Lincoln Highway, DeKalb, Illinois 60115, United States.
J Chem Educ. 2017 Mar 14;94(3):345-349. doi: 10.1021/acs.jchemed.6b00555. Epub 2017 Feb 13.
Drug design and discovery remains a popular topic of study to many students interested in visible, real-world applications of the chemical sciences. It is important that laboratory experiments detailing the early stages of drug discovery incorporate both compound design and an exploration of ligand/receptor interactions. Molecular modeling is widely employed in research endeavors seeking to predict the activity of potential compounds prior to synthesis and can therefore be used to illustrate these concepts. The following activity therefore details the use of AutoDock to predict the binding affinity and docked pose of a series of CDK2 inhibitors. Students can then compare their docking output to experimentally determined inhibitory activities and crystal structures. Finally, the AutoDock workflow detailed in this activity can be used in research settings, provided the receptor crystal structure is known.
药物设计与发现对于许多对化学科学的可见实际应用感兴趣的学生来说，仍然是一个热门的研究课题。重要的是，详细介绍药物发现早期阶段的实验室实验应包括化合物设计以及对配体/受体相互作用的探索。分子建模广泛应用于在合成前预测潜在化合物活性的研究工作中，因此可用于阐释这些概念。因此，以下活动详细介绍了使用AutoDock预测一系列CDK2抑制剂的结合亲和力和对接构象。然后，学生可以将他们的对接输出与实验确定的抑制活性和晶体结构进行比较。最后，如果已知受体晶体结构，本活动中详细介绍的AutoDock工作流程可用于研究环境。
