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

这项美国-匈牙利联合基金的研究项目“定量结构-活性关系和预测突变酶的QSAR的计算机模拟研究”将由Eotvos大学的Gabor Naray-Szabo博士与南加州大学的Arieh Warshel博士合作进行。最近在实验工作后形成的Similis Simili Gaudet原理指出，突变酶与其底物之间相似的(离子-离子、极性-极性和非极性-非极性)侧链相互作用比不同的(离子-极性、极性-非极性等)对过渡态稳定的贡献更大。一个。研究人员推测，这种效应可能与静电和疏水性酶-底物互补有关。为了详细了解这一现象并检验假说的普遍正确性，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，以便选择那些可能被解释为疏水互补的决定因素。匈牙利的Similis Simili Gaudet假说和美国方面开发和应用的模拟方法相结合，应该有助于我们对酶-底物相互作用的了解。这项化学研究实现了美国-匈牙利联合基金的计划目标，即通过使美国和匈牙利的顶尖专家能够结合互补的人才并在共同感兴趣和能力强的领域汇集研究资源来促进科学发展。

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.