From: pat@cs.albany.edu (Pat Keller)
Subject: SUNYA C. S. Dept. Colloquium
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Organization: The University at Albany, Comp. Sci. Dept.
Date: Thu, 19 Nov 1992 16:49:03 GMT
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                                     COLLOQUIUM

                University at Albany - State University of New York

                            Computer Science Department

                         Department of Biological Sciences

                 Computational Approaches to Side-Chain Prediction
                     in Proteins with Known Backbone Structures

                                     Hany Farid

                            Computer Science Department
                             University at Albany, SUNY

                  Friday, November 20, 1992 at 2:45pm in BIO 248*

                                      ABSTRACT

                 Two algorithms are presented for prediction  of  side  chain
            configurations  in  proteins with known backbone structures.  The
            first algorithm  predicts  side  chain  configurations  in  small
            buried  cores  and  the  second  predicts those configurations in
            entire proteins.  The  principle  difficulty  facing  side  chain
            prediction  algorithms  is  the combinatorial explosion of simul-
            taneously predicting even a small number (more than ten) of resi-
            dues.   One  strategy to overcome this combinatorial explosion is
            to greatly reduce the number of possible configurations  of  each
            residue type to only a few rotamer positions; this methodology is
            adopted in the work presented here.  In order to predict the side
            chain  configurations in protein cores, the number of unfavorable
            van der Waals contacts and the rotamer probability  are  computed
            for  every possible rotamer configuration.  It is then shown that
            one of the few configurations (less than 99.9999% of  all  confi-
            gurations)  with a small number of unfavorable van der Waals con-
            tacts and high rotamer probability is the "best" rotamer model of
            the  known  native  structure.   For the eight cores studied, the
            "best" rotamer models of the known native structure have an aver-
            age rms deviation of 0.477 Angstrom from their native structures.
            For entire proteins, it is computationally intractable to exhaus-
            tively  search  all  possible  rotamer configurations.  Simulated
            annealing and Monte Carlo  statistical  sampling  techniques  are
            employed  to  overcome  the  combinatorial explosion of searching

                                       - 2 -

            every rotamer configuration of an entire protein.  The prediction
            algorithm  "anneals"  to  a  minimum "energy state", then a Monte
            Carlo sampling of 10,000 configurations with energies within  one
            standard  deviation of this minimum energy is taken.  In order to
            predict side chain configurations, an  entropy  analysis  of  the
            Monte  Carlo  configurations  sampled  is performed.  The entropy
            analysis assigns to each residue a measure of confidence in pred-
            ictability;  if this measure is above a certain threshold a pred-
            iction is made, otherwise no attempt is made to predict the  side
            chain  configuration  of  the residue.  For the fifty proteins of
            known structure studied, on average, 62.8% of the side chain con-
            figurations are predicted with an accuracy of 71.7%.

            *Please note room change for this colloquia.

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