Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermodynamic and kinetic data from calorimetric titration measurements. The present study demonstrates the convenient collection of calorimetric data suitable for both thermodynamic and kinetic analysis for two series of congeneric ligands of human carbonic anhydrase II and correlates these findings with structural data obtained by macromolecular crystallography to shed light on the importance of shape complementarity for thermodynamics and kinetics governing a protein-ligand binding event. The study shows how minute chemical alterations change preferred ligand conformation and can be used to manipulate thermodynamic and kinetic signatures of binding. They give rise to the observation that analogous n-alkyl and n-alkyloxy derivatives of identical chain length swap their binding kinetic properties at unchanged binding affinity.

中文翻译：

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烷基链的构象变化决定了碳酸酐酶抑制剂的热力学和动力学结合曲线。

蛋白质-配体结合的热力学和动力学都是设计新型药物分子的重要方面。目前，热力学数据是用等温滴定热法收集的，而动力学数据主要来自表面等离振子共振。kinITC的新方法提供了量热滴定测量的热力学和动力学数据。本研究表明方便收集适用于人类碳酸酐酶II的两个同类配体的热力学和动力学分析的量热数据，并将这些发现与通过大分子晶体学获得的结构数据相关联，以阐明形状互补性对热力学的重要性和动力学控制蛋白质-配体结合事件。研究表明，微小的化学变化如何改变优选的配体构象，并可用于操纵结合的热力学和动力学特征。他们引起观察，相同链长的类似正烷基和正烷氧基衍生物以不变的结合亲和力交换其结合动力学性质。