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.

Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors / Poli, Giulio; Jha, Vibhu; Martinelli, Adriano; Supuran, Claudiu T; Tuccinardi, Tiziano. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 19:(2018), pp. 0-0. [10.3390/ijms19071851]

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

Supuran, Claudiu T;
2018

Abstract

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.
2018
19
0
0
Goal 3: Good health and well-being
Poli, Giulio; Jha, Vibhu; Martinelli, Adriano; Supuran, Claudiu T; Tuccinardi, Tiziano
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1308164
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