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

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...

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Autores principales: Poli, Giulio, Jha, Vibhu, Martinelli, Adriano, Supuran, Claudiu T., Tuccinardi, Tiziano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073570/
https://www.ncbi.nlm.nih.gov/pubmed/29937490
http://dx.doi.org/10.3390/ijms19071851
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author Poli, Giulio
Jha, Vibhu
Martinelli, Adriano
Supuran, Claudiu T.
Tuccinardi, Tiziano
author_facet Poli, Giulio
Jha, Vibhu
Martinelli, Adriano
Supuran, Claudiu T.
Tuccinardi, Tiziano
author_sort Poli, Giulio
collection PubMed
description 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.
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spelling pubmed-60735702018-08-13 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 Int J Mol Sci Article 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. MDPI 2018-06-23 /pmc/articles/PMC6073570/ /pubmed/29937490 http://dx.doi.org/10.3390/ijms19071851 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Poli, Giulio
Jha, Vibhu
Martinelli, Adriano
Supuran, Claudiu T.
Tuccinardi, Tiziano
Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors
title Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors
title_full Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors
title_fullStr Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors
title_full_unstemmed Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors
title_short Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors
title_sort development of a fingerprint-based scoring function for the prediction of the binding mode of carbonic anhydrase ii inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073570/
https://www.ncbi.nlm.nih.gov/pubmed/29937490
http://dx.doi.org/10.3390/ijms19071851
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