Entropy and Polarity Control the Partition and Transportation of Drug-like Molecules in Biological Membrane.

ABSTRACT: Partition and transportation of drug in the plasma membrane of a mammalian cell are the prerequisite for its function on target protein. Therefore, comprehensive understanding of the physicochemical properties and mechanism behind these complex phenomena is crucial in pharmaceutical research. By using the state-of-art molecular simulations with polarization effect implicitly or explicitly included, we studied the permeation behavior of 2-aminoethoxydiphenyl borate (2-APB), a broad-spectrum modulator for a number of membrane proteins. We showed that the protonation state and therefore the polarity of the drug is critical for its partition, and that the drug is likely to switch between different protonation states along its permeation pathway. By changing the degrees of freedom, protonation

SUBMITTER: Zhu Q 

PROVIDER: S-EPMC5735159 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature