Computer Simulation of Chemical Reactions in Synthetic Model Compounds andGenetically Engineered Active Sites

摘要

The main objective of this project is to advance our understanding of theprinciples of biological recognition and specificity by using computer simulation approaches. Such approaches are expected to be essential for detailed elucidation of the origin of the enormous power of biological catalysts and to help in exploiting the resulting insight in designing a new generation of highly specific molecular systems. Our computer simulation models have progressed to the level where we can reproduce the effect of genetic modifications of enzymes on its catalytic power in a semiquantitative way. We are also able to estimate in a reasonable way the overall catalytic effect of some enzymes. In three three years of this contract we have tried to exploit the fast accumulation of experimental information about genetically modified enzymes in developing clearer design principles. We have progressed in several directions toward this aim: (i) we explored a significant number of genetically modified enzymes (trypsin, subtilisin Aspartateiminotransferase and staphloccocal nucleases) and obtained more confidence in our predictive power. Keywords: Biological recognition, Enzyme catalysis, Computer aided enzyme engineering, Catalytic antibodies, Synthetic active sites. (JES)