Thermodynamics of Site-Specific Binding Processes in Biological Macromolecules

9406103 Di Cera在拟议的研究项目中，我们计划继续发展位点特异性结合效应的热力学理论。 我们有双重目标。 首先，我们试图提供一个概念框架和有效的策略，以利用实验解剖的网站特定的影响实验。 第二，我们试图通过揭示与其他子系统相互作用的子系统行为的热力学基础，将生物学中的合作效应分析提升到一个全新的水平。 这是统计热力学中的一个基本问题，由于其数学上的复杂性，它在很大程度上仍然是未公式化和未探索的。 如果不对局部效应进行热力学处理，我们对生物学中最令人兴奋和最具挑战性的问题，如协同性、分子识别和蛋白质折叠的理解必然是不完整的。 我们的项目需要发展一个生物学中相互作用系统的理论。 我们的目标是了解一个新的概念框架的蛋白质配体和蛋白质蛋白质识别的详细基础。 蛋白质介导的分子识别在生物学的几乎每个方面都是至关重要的一步，在分子水平上也是疾病发生、传播和控制的关键步骤。 拟议研究项目的进展将使我们更深入地了解蛋白质如何工作。 这将最终促进在药理学一级制定控制疾病的新战略。 ***

9406103 Di Cera In the proposed research project we plan to continue to develop the thermodynamic theory of site-specific binding effects. We have a dual goal in mind. First, we seek to provide experimentalists with a conceptual framework and effective strategies to be exploited in the experimental dissection of site-specific effects. Second, we seek to bring the analysis of cooperative effects in biology to a whole new level by unraveling the thermodynamic foundations of the behavior of subsystems open to interactions with other subsystems. This is a basic problem in statistical thermodynamics which remains in largest measure unformulated and unexplored, due to its mathematical complexity. Without a thermodynamic treatment of local effects, our understanding of the most exciting and challenging problems in biology, such as cooperativity, molecular recognition and protein folding, will remain necessarily incomplete. %%% Our project entails the development of a theory for interacting systems in biology. The goal is to understand the detailed basis for protein-ligand and protein-protein recognition in terms of a novel conceptual framework. Protein-mediated molecular recognition is a crucial step in nearly every aspect of biology, as well as in the onset, propagation and control of diseases at the molecular level. The developments under the proposed research project will provide us with a much deeper understanding of how proteins work. This will eventually foster the developments of new strategies for the control of diseases at the pharmacological level. ***