This US-Hungary Joint Fund research project on "Quantitative Structure-Activity Relationships and Computer Simulation Studies for the Prediction of Mutant Enzyme Spec. QSAR for Mutant Enzymes" will be conducted by Dr. Gabor Naray-Szabo of Eotvos University in cooperation with Dr. Arieh Warshel of the University of Southern California. The similis simili gaudet principle, formulated recently after experimental work, states that similar (ionic-ionic, polar-polar, and apolar-apolar) side-chain interactions between a mutant enzyme and its substrate contribute more to the transition-state stabilization than dissimilar (ionic-polar, polar- apolar, etc.) ones. The researchers postulate that the effect can be related to electrostatic and hydrophobic enzyme-substrate complementarity. To understand the phenomenon in detail and to check the general validity of the hypothesis, the researchers intend to perform both simple empirical and sophisticated molecular dynamics calculations on various enzyme-substrate systems and analyze energy terms in order to select those which may be interpreted as determinant of the hydrophobic complementarity. The combination of the similis simili gaudet hypothesis coming from Hungary and the simulation methods developed and applied by the American side should contribute to our knowledge of enzyme-substrate interactions. This research in chemistry fulfills the US-Hungary Joint Fund's program objective of advancing science by enabling leading experts in the United States and Hungary to combine complementary talents and pool research resources in areas of strong mutual interest and competence.
