Accurate Prediction of Ligand Affinities for a Proton-Dependent Oligopeptide Transporter.

ABSTRACT: Membrane transporters are critical modulators of drug pharmacokinetics, efficacy, and safety. One example is the proton-dependent oligopeptide transporter PepT1, also known as SLC15A1, which is responsible for the uptake of the ?-lactam antibiotics and various peptide-based prodrugs. In this study, we modeled the binding of various peptides to a bacterial homolog, PepT(St), and evaluated a range of computational methods for predicting the free energy of binding. Our results show that a hybrid approach (endpoint methods to classify peptides into good and poor binders and a theoretically exact method for refinement) is able to accurately predict affinities, which we validated using proteoliposome transport assays. Applying the method to a homology model of PepT1 suggests that the approach re

SUBMITTER: Samsudin F 

PROVIDER: S-EPMC4760754 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature