动力学
降级(电信)
泛素连接酶
热力学
蛋白质降解
三元运算
三元络合物
化学
反应速率常数
离解(化学)
动能
泛素
生物物理学
物理化学
物理
生物
生物化学
计算机科学
酶
电信
量子力学
基因
程序设计语言
作者
Hongtao Zhao,Frank Narjes
出处
期刊:ChemMedChem
[Wiley]
日期:2023-11-13
卷期号:18 (24)
被引量:1
标识
DOI:10.1002/cmdc.202300530
摘要
Abstract Kinetics of the PROTAC‐induced protein degradation were modelled using the equilibrium approximation, accounting for the protein recovery rate with a time lag. The simulated kinetic curves resemble what is experimentally observed, and the physical formulas of the half‐maximal degradation concentration (DC 50 ) were derived from them. The equations reveal that DC 50 is proportional to the dissociation constant of the ternary complex ( K d ) and inversely proportional to the expression level of the E3 ligase and the effective ubiquitylation rate ( k ub ). The predicted relationships were rigorously confirmed by experimental evidences from a matched molecular pair analysis using a set of published PROTACs.
科研通智能强力驱动
Strongly Powered by AbleSci AI