IPRO+/-: a computational protein design tool allowing not only for amino acid changes but also insertions and deletions

Conference Dates

September 15-19, 2019


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 (see

Figure 1). 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.

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