Next Article in Journal
Pathogenomics of Endometriosis Development
Next Article in Special Issue
Comparison of the Anion Inhibition Profiles of the α-CA Isoforms (SpiCA1, SpiCA2 and SpiCA3) from the Scleractinian Coral Stylophora pistillata
Previous Article in Journal
Evolutionary History of the Glycoside Hydrolase 3 (GH3) Family Based on the Sequenced Genomes of 48 Plants and Identification of Jasmonic Acid-Related GH3 Proteins in Solanum tuberosum
Previous Article in Special Issue
The Crystal Structure of a hCA VII Variant Provides Insights into the Molecular Determinants Responsible for Its Catalytic Behavior
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle

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

1
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
2
NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino, 50019 Florence, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 1851; https://doi.org/10.3390/ijms19071851
Received: 26 May 2018 / Revised: 16 June 2018 / Accepted: 20 June 2018 / Published: 23 June 2018
  |  
PDF [2553 KB, uploaded 23 June 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. View Full-Text
Keywords: carbonic anhydrase II inhibitor; docking; scoring function carbonic anhydrase II inhibitor; docking; scoring function
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Poli, G.; Jha, V.; Martinelli, A.; Supuran, C.T.; Tuccinardi, T. Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors. Int. J. Mol. Sci. 2018, 19, 1851.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top