Biomolecular Recognition and Binding Mechanisms

结合机制对蛋白质的功能非常重要。通过分子动力学模拟，我们研究了蛋白质从开放形式到闭合形式的路径，对于这种蛋白质，有大量的构象变化的实验数据。对于我们研究的几种酶，出现了一系列事件，与实验一致，并且在保守的数据库位置和识别的灵活区域之间具有显著的相关性。尽管结构和功能不同，但我们观察到一种保守的机制。 蛋白质通过结合发挥作用。我们的目标是预测蛋白质-蛋白质和蛋白质-配体相互作用的结合模式。此外，我们的目标是预测这些，即使有重大的结构变化，或者如果输入是模型化的(基因组)数据。我们的工作有两个方向。首先，以一种不受分子表面精细特征影响的方式来表征结合部位。第二，设计灵活的对接算法。首先，我们研究了蛋白质表面的残基“热点”，并探索了组合噬菌体展示文库。对于第二个，我们继续开发允许铰链弯曲运动的对接算法。

Binding mechanisms are extremely important for protein function. Through molecular dynamics simulations, we study the path from the open to the closed form in a protein for which there are experimental data for a large conformational change. For several enzymes we have studied, a series of events emerges, consistent with experiment and with a striking correlation between conserved database positions and identified flexible regions. Despite the dissimilar structure, and function, we observe a conserved mechanism. Proteins function through binding. Our goal is to predict binding modes of protein-protein and protein-ligand sociations. Further, our goal is to predict these even if there are significant structural changes, or if the input are modeled (genomic) data. Our work is in two directions. First, to characterize binding sites in a way that is immune to the fine features of the molecular surface. And second to devise flexible docking algorithms. For the first, we study residue "hot spots" on the protein surface and explore combinatorial phage display libraries. For the second, we continue the development of docking algorithms which allow hinge-bending motions.