pH-low insertion peptides (pHLIPs) can insert into membrane and form a stable a-helix when introduced to acidic environments adjacent to the tumor cells. With few variants with pH-selectivity available as cancer imaging tools, there is a need to develop computational procotols to help design new pHLIP variants. To understand the design principle, we first investigated the effects of pKa shifts in wild type pHLIP and the V7 variant using different types of Constant pH Molecular Dynamics (CpHMD) simulations. Next, we investigated multiple protonation states of both wt-PHLIP and V7and examined the variation of the energy penalty of insertion from potential-of-mean-force (PMF) simulations. This study provides a computational approach to aid the development of rationally designed peptides and to contribute to our understanding of the membrane insertion mechanism.

Towards a rational design of pHLIP via constant pH molecular dynamics and free energy simulations

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.