Dynamic Protonation Dramatically Affects the Membrane Permeability of Drug-like Molecules.

ABSTRACT: Permeability (P_m) across biological membranes is of fundamental importance and a key factor in drug absorption, distribution, and development. Although the majority of drugs will be charged at some point during oral delivery, our understanding of membrane permeation by charged species is limited. The canonical model assumes that only neutral molecules partition into and passively permeate across membranes, but there is mounting evidence that these processes are also facile for certain charged species. However, it is unknown whether such ionizable permeants dynamically neutralize at the membrane surface or permeate in their charged form. To probe protonation-coupled permeation in atomic detail, we herein apply continuous constant-pH molecular dynamics along with free energ

SUBMITTER: Yue Z 

PROVIDER: S-EPMC6755907 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature