Understanding Passive Membrane Permeation of Peptides: Physical Models and Sampling Methods Compared

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Mar 11

PMID 36902455

Authors

Liuba Mazzanti

Tap Ha-Duong

Affiliations

Soon will be listed here.

Abstract

The early characterization of drug membrane permeability is an important step in pharmaceutical developments to limit possible late failures in preclinical studies. This is particularly crucial for therapeutic peptides whose size generally prevents them from passively entering cells. However, a sequence-structure-dynamics-permeability relationship for peptides still needs further insight to help efficient therapeutic peptide design. In this perspective, we conducted here a computational study for estimating the permeability coefficient of a benchmark peptide by considering and comparing two different physical models: on the one hand, the inhomogeneous solubility-diffusion model, which requires umbrella-sampling simulations, and on the other hand, a chemical kinetics model which necessitates multiple unconstrained simulations. Notably, we assessed the accuracy of the two approaches in relation to their computational cost.

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