Title: The Effect of Amino Acids Positional Determinacy in Proteins

Speaker: Dr. Sergey Chesnokov, Professor, State Higher School of Economics (Moscow, Russia), and Research Director, Context Co., Ltd., and Associate Editor, Sociological Journal, Russian Academy of Sciences

Date/Time: Tuesday August 8th, 2006, 3pm, SDSC Auditorium

Host: Ilya Zaslavsky (zaslavsk@sdsc.edu)

Abstract: Naturally occurring polypeptide sequences occupy only a tiny fraction of all possible combination of 20 common amino acids (a.a.) However, random polypeptides are misfolded making de novo design of protein structures or functions challenging even with known protein domains. Indeed, the rules determining why a particular sequence of a.a. is present or absent in a protein are not known. This talk will present novel methods for discovering rules of a.a. positioning, and the rule systems uncovered in analysis of several protein databases.
Several model protein sets (~500 human proteins) were analyzed using Determinacy analysis techniques, to discover numerous a.a. configurations that predetermine the presence of other amino acid configurations in the same sequences. This phenomenon was called the effect of positional determinacy of amino acids, or “PDA” effect. Over 1900 positioning rules were found to be exemplified in 19 or more instances throughout the protein database. In more than 90% of all rules found, the 4 surrounding amino acids are necessary and sufficient to determine the presence of a determinable amino acid at that position. Remarkably, all regularities describe above disappear in the randomized copy of the same protein database. Thus, large numbers of PDA rules operating in the source base cannot be attributed to chance. A theoretical mechanism of a random generation of PDA rules consistent with experience is presented.

Dr. Chesnokov is an expert in mathematical methods for data analysis, and the creator of Determinacy Analysis and Logic techniques and software. The approach has been widely used for data analysis in medical and biological databases, as well as in sociology, economics and the earth sciences. The presentation is one of the outcomes of his recent sabbatical at EPFL in Lausanne.