An optimization approach to protein structure prediction
Betty Eskow
Dept of Computer Science,
University of Colorado,
Boulder, CO 80309-0430
eskow@cs.colorado.edu
http://www.cs.colorado.edu/~eskow
Abstract
In this talk we discuss an attack on the problem of protein structure
prediction by parallel global optimization techniques. The protein
structure prediction problem is one of the fundamental challenges of
modern science. It is to predict the three-dimensional shape, or
native state of a protein, given its sequence of amino-acids.
Optimization is one of the promising approaches to solving this
problem, because it is believed that in most cases, the native state
corresponds to the minimum free energy of the protein. However, the
energy landscape of a realistic-sized protein has thousands of
parameters and an enormous number of local minimizers. This means
that an efficient global optimization approach for very large scale
problems that includes intelligent use of the structure of the
problem, coupled with efficient use of multiple processors, is
necessary to solve the problem.
We describe a large-scale, stochastic-perturbation global optimization
algorithm used for determining the structure of proteins. The method
incorporates secondary structure predictions (which describe the more
basic elements of the protein structure) into the starting structures,
and thereafter minimizes using a purely physics-based energy model.
We have tested our approach in CASP competition, where many research
groups compete in prediction of structures that have just been
experimentally determined. Results show our method to be particularly
successful on protein targets where structural information from
similar proteins is unavailable, i.e., the most difficult targets for
most protein structure prediction methods.