(176b) Ipro+/-: A Computational Protein Design Tool Allowing NOT ONLY for Amino Acid Changes but Also Insertions and Deletions

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

Ratul
Chowdhury, Department of Chemical Engineering. The Pennsylvania State
University, University Park, Pennsylvania 16802, United States

ratul@psu.edu

Matthew
J Grisewood, Department of Chemical Engineering. The Pennsylvania State
University

John
Brezovec, Department of Chemical Engineering. The Pennsylvania State University

Costas
D Maranas, Department of Chemical Engineering. The Pennsylvania State
University

Key Words:       protein, computational protein design,
indels, mutation, optimization

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.