Protonation Enhances the Inherent Helix-Forming Propensity of pHLIP.

ABSTRACT: Cell-penetrating peptides (CPPs) can be potentially used in targeted delivery of therapeutic cargoes. However, their conformation in solution is poorly understood. We employed molecular dynamics simulations to probe the structural fluctuations of an anionic CPP, pH Low Insertion Peptide (pHLIP), in solution to determine the effects of modifications to selected residues on the structure of pHLIP. Two types of modifications were tested: (1) protonation of aspartic acid residues and (2) point mutations known to affect the acid sensitivity of pHLIP. pHLIP samples conformations ranging from coil to helix to sheet, and modifications to pHLIP lead to subtle shifts in the balance between these conformations. In some instances, pHLIP is as likely to form a helical conformation as it is to form an u

SUBMITTER: Gupta C 

PROVIDER: S-EPMC5709774 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature