变构药物中的驻留时间是如何起作用的。
How residence time works in allosteric drugs.
作者信息
Nussinov Ruth, Jang Hyunbum
机构信息
Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Cancer Innovation Laboratory, National Cancer Institute, Frederick, MD 21702, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Cancer Innovation Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
出版信息
Curr Opin Struct Biol. 2025 Aug 29;94:103149. doi: 10.1016/j.sbi.2025.103149.
Drug residence time defines the duration the drug is bound to its protein target. It is a crucial determinant of drug action. Yet, a priori estimating it in the design could be the most challenging. The mechanisms of allosteric and orthosteric drugs differ in how they affect it. Binding at the active site, the residence time of orthosteric drugs is primarily affected by binding kinetics, which is not the case for allosteric drugs. Allosteric drugs determine the orthosteric drug residence time by the nature and extent of the population shift that they promote, which modulate the active site conformation. However, cooperative binding is bidirectional; orthosteric drug binding at the active site can increase (decrease) residence time at the allosteric site.
药物驻留时间定义了药物与蛋白质靶点结合的持续时间。它是药物作用的关键决定因素。然而，在设计过程中先验估计它可能是最具挑战性的。变构药物和正构药物影响药物驻留时间的机制不同。正构药物在活性位点结合时，其驻留时间主要受结合动力学影响，变构药物则不然。变构药物通过它们促进的群体转移的性质和程度来决定正构药物的驻留时间，这种群体转移会调节活性位点的构象。然而，协同结合是双向的；正构药物在活性位点的结合可以增加（减少）在变构位点的驻留时间。
Zotero 插件