Bioinformatics and statistical mechanics of molecular systems

The research proposed in the program entitled "Bioinformatics and statistical mechanics of molecular systems" has interdisciplinary character since the research activities are placed within the area of chemistry, molecular biology and statistical physics, with the main emphasis on bioinformatics. The field of bioinformatics is getting more and more attention, especially due to the importance of the results of the Human Genome project which is rapidly approaching the state of completion. The enormous potential value of the results provided by the Human Genome project will be exploited also in the course of the research in the framework of the present research program. The work will proceed along several lines. DNA sequences from the genetic sequence data bases will be used and various types of the analysis will be performed. By aligning the sequences of orthologous and paralogous genes the reconstruction of the mutational events will be performed. The results will be analysed in the framework of models based on statistical physics. As the output of such analyses one can expect that the results will emerge which will have the relevance to fundamental questions regarding the molecular evolution and function of the gene products. For the purpose of maximal efficiency of statistical elaboration of the results of DNA sequence analyses the development of the statistical mechanics methodologies will be also pursued in the framework of the present research program. In parallel the work will proceed along the standard lines of rational drug design. The structure of enzyme - ligand complex at the active site will be studied. The methods of molecular mechanics, molecular dynamics and ab initio methods of electronic structure determination will be used. The design of new inhibitors of various enzymes (serine protease, beta-lactamase, DNA gyrase) will be approached.