Development of GRAMM Method and Software for Protein-Protein Docking

该项目的主要目标是获得一种方法，该方法将从两个独立的，灵活的和可能不准确的蛋白质结构中产生蛋白质-蛋白质复合物的精确模型。 这种新的对接程序的一个显着特点是，除了两种蛋白质的相对位置之外，它还搜索每个蛋白质的构象。 该项目涉及GRAMM（全球范围分子匹配）对接方法和软件的蛋白质对接的进一步发展。 GRAMM在低分辨率下用于预测蛋白质复合物的非冗余数据库中复合物的结构，使用复合物及其模型的实际单个结构。 柔性对接程序预计将是更准确和更强大的相互作用的蛋白质的初始近似结构的不准确性比目前流行的刚性对接程序。 鉴于人类基因组计划的进展速度，这种方法将特别有用，因为它将允许快速评估大量预测蛋白质结构的功能。 因此，蛋白质结构预测和蛋白质对接的结合有望大大提高分子建模的实用性。

The main goal of this project is to obtain a method which will produce an accurate model of a protein-protein complex from two separate, flexible, and possible inaccurate protein structures. A distinguishing feature of this new docking procedure is that it searches through the conformation of each protein in addition to the relative positions of the two proteins. This project involves the further development of GRAMM (Global RAnge Molecular Matching) docking methodology and software for protein docking. GRAMM is used at low resolution to predict the structures of complexes in the non-redundant database of protein complexes using both actual individual structures from the complexes and their models. The flexible docking procedure is expected to be more accurate and more robust with respect to the inaccuracies in the initial approximate structures of the interacting proteins than are the currently prevalent rigid docking procedures. The approach will be especially useful in view of the rate of advance in the human genome project, since it will allow a rapid evaluation of functions for a large number of predicted protein structures. Thus, the combination of protein structure prediction and protein docking is expected to increase greatly the usefulness of molecular modeling.