In silico prediction of mutant HIV-1 proteases cleaving a target sequence
Abstract
HIV-1 protease represents an appealing system for directed enzyme re-design, since it has various different endogenous targets, a relatively simple structure and it is well studied. Recently Chaudhury and Gray (Structure (2009) 17: 1636 -- 1648) published a computational algorithm to discern the specificity determining residues of HIV-1 protease. In this paper we present two computational tools aimed at re-designing HIV-1 protease, derived from the algorithm of Chaudhuri and Gray. First, we present an energy-only based methodology to discriminate cleavable and non cleavable peptides for HIV-1 proteases, both wild type and mutant. Secondly, we show an algorithm we developed to predict mutant HIV-1 proteases capable of cleaving a new target substrate peptide, different from the natural targets of HIV-1 protease. The obtained in silico mutant enzymes were analyzed in terms of cleavability and specificity towards the target peptide using the energy-only methodology. We found two mutant proteases as best candidates for specificity and cleavability towards the target sequence.
Keywords
Cite
@article{arxiv.1404.0188,
title = {In silico prediction of mutant HIV-1 proteases cleaving a target sequence},
author = {Jan H. Jensen and Martin Willemoës and Jakob R. Winther and Luca De Vico},
journal= {arXiv preprint arXiv:1404.0188},
year = {2014}
}