COMPUTER STUDIES OF PROTEIN SURFACE RECOGNITION

蛋白质表面识别的计算机研究

• 批准号: 3285143
• 负责人: MICHAEL L CONNOLLY
• 金额: $ 11.15万
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3285143
• 关键词: antibody; chemical binding; chemical bond; computer graphics /printing; molecular shape; nucleic acids; surface property; trypsin inhibitors

Proteins and other biological macromolecules interact with each other in specific ways. This specificity is determined by the geometric arrangement and chemical properties of atoms at the surfaces of the interacting molecules. A detailed description of the molecular surface can be produced by a combination of X-ray crystallographic structure determination, solvent-accessibility calculations and computer graphics. This detailed molecular surface description can be applied to understanding systems where macromolecules interact, for example: the binding of an antibody molecule to a protein, the binding of gene regulatory proteins to DNA, the aggregation of hemoglobin subunits to form the tetrameric protein, the blocking of the active sites of trypsin and carboxypeptidase enzymes by inhibitor proteins, and the assembly of viral coat protein monomers into capsids. Molecular recognition is dependent on both chemical and geometric complementarity between the surface regions forming the contact. Chemical complementarity can be investigated by analyzing hydrogen bonds, salt links and hydrophobic contacts at molecular interfaces. Geometric complementarity can be studied by characterizing the shapes of the outer surfaces of macromolecules. The outer surface of a protein is computed by rolling a sphere, representing a water molecule, over the three-dimensional structure of the protein. For each region of protein surface, a set of parameters characterizing the shape of the region should then be computed. For the situation where molecules have been co-crystallized and the atomic structure of the complex has been determined, the geometric complementarity at the interface would be measured by comparing the shape parameters of the surface regions in contact. Ultimately, it should be possible to predict associations between pairs of proteins, or between a protein and a nucleic acid, by computationally docking together surface regions with complementary shapes. This ability would be very useful, since it would augment the amount of structural information known, without requiring any additional crystallographic work.

蛋白质和其他生物大分子相互作用， 具体方式。 这种特异性是由几何排列决定的 和化学性质的原子在表面的相互作用 分子。 可以产生分子表面的详细描述 通过X射线晶体结构测定的组合， 溶剂可及性计算和计算机图形。 该详细 分子表面描述可用于理解系统， 大分子相互作用，例如： 基因调控蛋白与DNA的结合， 血红蛋白亚基聚集形成四聚体蛋白， 通过阻断胰蛋白酶和羧肽酶的活性位点， 抑制蛋白，以及病毒外壳蛋白单体组装成 衣壳 分子识别依赖于化学和几何 形成接触的表面区域之间的互补性。 化学 互补性可以通过分析氢键、盐键 和分子界面处的疏水接触。 几何 互补性可以通过表征外部的形状来研究。 大分子表面。 蛋白质的外表面是通过 滚动一个代表水分子的球体， 蛋白质的结构。 对于蛋白质表面的每个区域， 然后应该计算表征该区域形状的参数。 对于分子已经共结晶并且原子 配合物的结构已确定，几何互补性 在界面处将通过比较 接触的表面区域。 最终，我们应该可以预测 蛋白质对之间或蛋白质与核酸之间的关联 酸，通过计算对接表面区域与 互补的形状 这种能力非常有用，因为它 增加已知的结构信息量，而不需要任何 额外的晶体学工作。