Development of a Fingerprint-Based Scoring Function for the Prediction of the Binding Mode of Carbonic Anhydrase II Inhibitors.
Int J Mol Sci
; 19(7)2018 Jun 23.
Article
em En
| MEDLINE
| ID: mdl-29937490
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 ligandâ»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 ligandâ»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 ligandâ»protein interaction fingerprints showed a useful application in the binding mode analysis of structurally diverse CAII ligands.
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Base de dados:
MEDLINE
Assunto principal:
Projetos de Pesquisa
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Sulfonamidas
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Mapeamento de Peptídeos
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Inibidores da Anidrase Carbônica
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Anidrase Carbônica II
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article