Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors

作者：Poli Giulio; Jha Vibhu; Martinelli Adriano; Supuran Claudiu T; Tuccinardi Tiziano^*

来源：International Journal of Molecular Sciences, 2018, 19(7): 1851.

DOI：10.3390/ijms19071851

• carbonic anhydrase II inhibitor
• docking
• scoring function

Carbonic anhydrase II (CAII) is a zinc-containing metalloenzyme whose aberrant activity is associated with various diseases such as glaucoma, osteoporosis, and different types of tumors; therefore, the development of CAII inhibitors, which can represent promising therapeutic agents for the treatment of these pathologies, is a current topic in medicinal chemistry. Molecular docking is a commonly used tool in structure-based drug design of enzyme inhibitors. However, there is still a need for improving docking reliability, especially in terms of scoring functions, since the complex pattern of energetic contributions driving ligand-protein binding cannot be properly described by mathematical functions only including approximated energetic terms. Here we report a novel CAII-specific fingerprint-based (IFP) scoring function developed according to the ligand-protein interactions detected in the CAII-inhibitor co-crystal structures of the most potent CAII ligands. Our IFP scoring function outperformed the ability of Autodock4 scoring function to identify native-like docking poses of CAII inhibitors and thus allowed a considerable improvement of docking reliability. Moreover, the ligand-protein interaction fingerprints showed a useful application in the binding mode analysis of structurally diverse CAII ligands.

• 出版日期2018-7