Kumar Sivakumar Prasanth, Jasrai Yogesh T, Pandya Himanshu A
Department of Bioinformatics, Applied Botany Centre (ABC), Ahmedabad-380009, Gujarat, India.
Curr Comput Aided Drug Des. 2016;12(1):15-28. doi: 10.2174/1573409912666160104130012.
Inverse (or reverse) docking approach which involves docking of a ligand against a set of protein structures to predict possible protein target(s), possess limitations, including inefficient empirical scoring schemes and similarities in protein active site shape and physico-chemical properties. To overcome this limitation, we combined receptor- and ligand-based methods to predict probable protein targets. We showed that the experimental protein target along with possible offtargets can be effectively retrieved if the docking energy of the reference molecule and probe molecules based scaled energy profiles were combined and clustered together. The present method was validated using 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines that inhibit Candida albicans dihydrofolate reductase (DHFR) in vitro.
反向（或逆向）对接方法是将配体与一组蛋白质结构进行对接以预测可能的蛋白质靶点，但该方法存在局限性，包括低效的经验评分方案以及蛋白质活性位点形状和物理化学性质的相似性。为克服这一局限性，我们结合了基于受体和配体的方法来预测可能的蛋白质靶点。我们表明，如果将参考分子和探针分子基于比例能量分布的对接能量进行合并和聚类，就可以有效地检索到实验性蛋白质靶点以及可能的脱靶。本方法使用在体外抑制白色念珠菌二氢叶酸还原酶（DHFR）的7,8 - 二烷基 - 1,3 - 二氨基吡咯并[3,2 - f]喹唑啉进行了验证。
