化学
生物物理学
位阻效应
罗丹明
基质(水族馆)
分子动力学
结合位点
流出
脂质双层
P-糖蛋白
罗丹明B
罗丹明123
立体化学
结晶学
膜
生物化学
计算化学
荧光
地质学
多重耐药
催化作用
物理
海洋学
抗生素
生物
光催化
量子力学
作者
Christian Jorgensen,Martin B. Ulmschneider,Peter C. Searson
标识
DOI:10.1021/acs.jmedchem.3c01069
摘要
We report molecular dynamics simulations of rhodamine entry into the central binding cavity of P-gp in the inward open conformation. Rhodamine can enter the inner volume via passive transport across the luminal membrane or lateral diffusion in the lipid bilayer. Entry into the inner volume is determined by the aperture angle at the apex of the protein, with a critical angle of 27° for rhodamine. The central binding cavity has an aqueous phase with a few lipids, which significantly reduces substrate diffusion. Within the central binding cavity, we identified regions with relatively weak binding, suggesting that the combination of reduced mobility and weak substrate binding confines rhodamine to enable the completion of the efflux cycle. Tariquidar, a P-gp inhibitor, aggregates at the lower arms of the P-gp, suggesting that inhibition involves steric hindrance of entry into the inner volume and/or steric hindrance of access of ATP to the nucleotide-binding domains.
科研通智能强力驱动
Strongly Powered by AbleSci AI