U.S.-Italy Cooperative Research: The Role of Peptide Fragments of Proteins in Folding and Assembly

该奖项将支持康奈尔大学的Harold Scheraga教授和西奈山医学院的George Nemethy教授与意大利那不勒斯大学的Adriana Zagari教授进行研究合作。合作的目的是确定形成蛋白质结构和功能重要部分的几个短肽的首选构象。将调查两个具体问题。第一个问题是胶原蛋白的非螺旋端肽。这些多肽通过与聚集体中邻近分子的特定相互作用，在引导和稳定胶原蛋白的特定组装方式方面发挥着重要作用。第二个问题涉及牛胰腺和精液核糖核酸酶中的几种多肽，并已被提出在这些分子的折叠过程中发挥作用。这两项研究的目的都是为了确定多肽与蛋白质分子其余部分相互作用的性质，从而了解它们在天然蛋白质折叠和组装中的作用。多肽的优选构象将通过构象能量计算、X射线结晶学、核磁共振和荧光测量来确定。聚集体中分子之间的原子间相互作用将通过能量计算来模拟。多肽合成和溶液的物理化学测量将在康奈尔大学的谢拉加实验室进行。结晶和X射线结构测定将由Zagari在那不勒斯进行。构象能量计算将由所有三个小组进行，由西奈山的Nemethy协调。项目的规划和结果的解释将需要理论方法和实验方法相结合。

This award will support Professor Harold Scheraga of Cornell University and Professor George Nemethy of the Mount Sinai School of Medicine in a research collaboration with Professor Adriana Zagari of the University of Naples, Italy. The purpose of the collaboration is the determination of the preferred conformations of several short peptides that form structurally and functionally important parts of proteins. Two specific problems will be investigated. The first problem is that of the nonhelical telopeptides of collagen. These peptides play an important role in directing and stabilizing the particular manner of assembly of collagen, by means of specific interactions with neighboring molecules in aggregates. The second problem concerns several peptides that occur in bovine pancreatic and seminal ribonucleases and have been proposed to play a role in the folding process of these molecules. The aim of both of these investigations is to establish the nature of the interactions of the peptides with the rest of the protein molecule and thereby understand their role in the folding and assembly of native proteins. Preferred conformations of the peptides will be determined by conformational energy computations, X-ray crystallography, and NMR and fluorescence measurements. Interatomic inter- actions between molecules in aggregates will be modeled by energy computations. Peptide synthesis and solution physicochemical measurements will be carried out in Scheraga's laboratory at Cornell. Crystallization and X-ray structural determination will be done by Zagari in Napoli. Conformational energy computations will be carried out by all three groups, coordinated by Nemethy at Mount Sinai. The planning of the project and the interpretation of the results will require the combination of theoretical and experimental approaches.