U.S.-Hungary Joint Fund Research on Quantitative Structure- Activity Relationships for Mutant Enzymes

美国-匈牙利联合基金项目“突变酶QSAR预测的定量构效关系和计算机模拟研究”将由厄特沃斯大学的Gabor Naray-Szabo博士与南加州大学的Arieh Warshel博士合作进行。最近在实验工作后提出的similis simili gaudet原理指出，突变酶与其底物之间相似的侧链相互作用（离子-离子、极性-极性和极性-极性）比不同的侧链相互作用（离子-极性、极性-极性等）更有助于过渡状态的稳定。研究人员推测，这种效应可能与静电和疏水酶-底物互补性有关。为了详细了解这一现象并检查假设的一般有效性，研究人员打算对各种酶-底物系统进行简单的经验和复杂的分子动力学计算，并分析能量项，以选择那些可能被解释为疏水互补性的决定因素。匈牙利的similis simili gaudet假说与美国方面开发和应用的模拟方法相结合，应该有助于我们了解酶-底物相互作用。这项化学研究实现了美国-匈牙利联合基金推进科学的计划目标，使美国和匈牙利的顶尖专家能够在共同感兴趣和能力强的领域结合互补的人才和集中的研究资源。

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.