Polar/apolar interfaces modulate the conformational behavior of cyclic peptides with impact on their passive membrane permeability.

ABSTRACT: Cyclic peptides have the potential to vastly extend the scope of druggable proteins and lead to new therapeutics for currently untreatable diseases. However, cyclic peptides often suffer from poor bioavailability. To uncover design principles for permeable cyclic peptides, a promising strategy is to analyze the conformational dynamics of the peptides using molecular dynamics (MD) and Markov state models (MSMs). Previous MD studies have focused on the conformational dynamics in pure aqueous or apolar environments to rationalize membrane permeability. However, during the key steps of the permeation through the membrane, cyclic peptides are exposed to interfaces between polar and apolar regions. Recent studies revealed that these interfaces constitute the free energy minima of the permeation

SUBMITTER: Linker SM 

PROVIDER: S-EPMC8981571 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature