IPRO+/-: A COMPUTATIONAL PROTEIN DESIGN TOOL ALLOWING NOT ONLY FOR AMINO ACID CHANGES BUT ALSO INSERTIONS AND DELETIONS

摘要

The need for enzymes with new or improved catalytic properties and specificities underpins many challenges in both biotechnology and pharmaceutical industry. This is typically carried out by changing the native amino acid composition through single or multiple mutations or recombination. Many computational strategies have been developed for suggesting amino acid changes (i.e., mutations) likely to usher an altered substrate or cofactor specificity, improved thermostability or higher turnover. However, by perusing protein family alignments one can immediately notice the ubiquitous presence of gaps. These gaps imply that not all active enzyme variants have the same backbone length with insertions and deletions (indels) contributing significantly to the possibilities of altering enzyme activity by drastically affecting protein repacking. Currently, no algorithms exist which can systemically position multiple insertions or deletions during in silico protein redesign. In this contribution we introduce IPRO+/-, a first of its kind integrated environment for protein redesign with respect to a single or multiple binding imperatives by not only predicting amino acid changes, but also insertions and deletions . IPRO+/- allows the user to run standalone programs for (a) predicting energy minimized structural models of an enzyme with a desired indels and/or mutations, (b) computing binding free energies between proteins and small molecules, and (c) performing energy minimization on any protein or protein complex. The contribution will provide an overview of the tasks involved in IPRO+/-, input language terminology, algorithmic details, software implementation specifics and application highlights. IPRO+/- will be made freely downloadable from http://www.maranasgroup.com/software.htm upon publication.