Morton C J, Ladbury J E
Oxford Centre for Molecular Science, University of Oxford, New Chemistry Laboratory, UK.
Protein Sci. 1996 Oct;5(10):2115-8. doi: 10.1002/pro.5560051018.
The elucidation of a relationship between the thermodynamic parameters and the structural changes accompanying biomolecular interactions could lead to predictive algorithms. For example, based on some knowledge of the structure of a target molecule the affinities of ligands could be determined with obvious implications for the pharmaceutical industry. In attempting to relate the thermodynamic and structural changes on formation of a protein-DNA complex, the correlation between change in heat capacity and burial of surface area has proved successful. However, this correlation appears to break down when water molecules are included in the binding interface. Here we present data that support the hypothesis that bound water molecules have to be considered as contributing to the change in heat capacity and could, thus, be used in ligand design.
阐明热力学参数与生物分子相互作用伴随的结构变化之间的关系可能会产生预测算法。例如，基于对目标分子结构的一些了解，可以确定配体的亲和力，这对制药行业具有明显的意义。在试图关联蛋白质-DNA复合物形成时的热力学和结构变化时，已证明热容变化与表面积埋藏之间的相关性是成功的。然而，当结合界面中包含水分子时，这种相关性似乎就不成立了。在此，我们提供的数据支持这样一种假设，即结合的水分子必须被视为对热容变化有贡献，因此可用于配体设计。
