U.S.-Mexico Cooperative Science: Theoretical Investigation of Immunoglobulin Loop Structure

9416589 Hermans美洲项目奖将支持北卡罗莱纳大学教堂山分校的Jan Hermans博士和墨西哥国立自治大学的Francisco Lara Ochoa博士之间的合作研究项目，重点是抗体环结构的互补研究。基于分子动力学模拟的生物大分子构象稳定性研究方法将应用于伽玛球蛋白及相关分子的高变环的构象偏好问题。计算将被执行，以评估相对自由能的解决方案为不同的构象的特异性确定回路。本研究解决了两个重要的科学问题：免疫球蛋白环的序列和结构之间的关系以及在模拟的基础上区分蛋白质的替代构象的问题。在蛋白质工程和疾病的背景下，这些问题的答案将对理解新的免疫球蛋白序列的特性产生重要影响，并将是对所谓的蛋白质折叠问题的理论研究中有价值的最后一步，蛋白质折叠问题多年来一直是结构生物学的核心问题。＊＊＊

9416589 Hermans This Americas Program award will support a collaborative research project between Dr. Jan Hermans, University of North Carolina, Chapel Hill, and Dr. Francisco Lara Ochoa, Universidad Autonoma Nacional de Mexico, focusing on complementary studies of loop structures in antibodies. Methods for study of conformational stability of biological macromolecules with molecular dynamics simulation will be applied to problems of the conformational preferences of hypervariable loops of gamma globulins and related molecules. Calculations will be performed to assess the relative free energies in solution for different conformers of specificity determining loops. This research addresses two important scientific questions: the relation between sequence and structure of immunoglobulin loops and the problem of distinguishing alternate conformations of proteins on the basis of simulations. Answers to these questions will have important consequences for understanding the properties of new immunoglobulin sequences, in the context of protein engineering and disease, and would be a valuable final step in theoretical studies of the so-called protein folding problem, which has been a central question in structural biology for many years. ***