Oda Akifumi
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai, Japan.
Yakugaku Zasshi. 2011;131(10):1429-35. doi: 10.1248/yakushi.131.1429.
Searching for the ligand-binding pockets of proteins plays an important role in structure-based drug design (SBDD), which is based on knowledge of the three-dimensional structures of target proteins. In SBDD, small molecules that can interact with the target protein are designed. SBDD methods require the identification of ligand-binding pockets, in which ligand molecules interact with protein atoms. The computer programs for the detection of ligand-binding pockets are categorized into two types: one is programs using only geometric properties; and the other is programs using the physicochemical properties of proteins as well as geometry. This paper describes the development and evaluation of a program for ligand-binding pocket search. The program HBOP (Hydropho Bicity On a Protein) searches for ligand-binding pockets using hydrophobic potentials derived from experimentally determined functions. This is based on the fact that hydrophobicity plays a significant role in protein-ligand binding. The results of evaluation indicate that programs using physicochemical properties can discover actual ligand-binding pockets more efficiently than those using only geometric properties.
寻找蛋白质的配体结合口袋在基于结构的药物设计（SBDD）中起着重要作用，该设计基于靶蛋白三维结构的知识。在SBDD中，设计能够与靶蛋白相互作用的小分子。SBDD方法需要识别配体结合口袋，配体分子在其中与蛋白质原子相互作用。用于检测配体结合口袋的计算机程序分为两类：一类是仅使用几何特性的程序；另一类是同时使用蛋白质物理化学特性和几何特性的程序。本文描述了一种用于配体结合口袋搜索程序的开发与评估。HBOP（蛋白质上的亲水性）程序利用从实验确定的函数导出的疏水势来搜索配体结合口袋。这是基于疏水性在蛋白质-配体结合中起重要作用这一事实。评估结果表明，使用物理化学特性的程序比仅使用几何特性的程序能更有效地发现实际的配体结合口袋。
