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Simple Coordination Geometry Descriptors Allow to Accurately Predict Metal-Binding Sites in Proteins
Sciortino, Giuseppe (Università di Sassari. Dipartimento di Chimica e Farmacia)
Garribba, Eugenio (Università di Sassari. Dipartimento di Chimica e Farmacia)
Rodríguez-Guerra Pedregal, Jaime (Universitat Autònoma de Barcelona. Departament de Química)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)

Date: 2019
Abstract: With more than a third of the genome encoding for metal-containing biomolecules, the in silico prediction of how metal ions bind to proteins is crucial in chemistry, biology, and medicine. To date, algorithms for metal-binding site prediction are mainly based on sequence analysis. Those methods have reached enough quality to predict the correct region of the protein and the coordinating residues involved in metal-binding, but they do not provide three-dimensional (3D) models. On the contrary, the prediction of accurate 3D models for protein-metal adducts by structural bioinformatics and molecular modeling techniques is still a challenge. Here, we present an update of our multipurpose molecular modeling suite, GaudiMM, to locate metal-binding sites in proteins. The approach is benchmarked on 105 X-ray structures with resolution lower than 2. 0 Å. Results predict the correct binding site of the metal in the biological scaffold for all the entries in the data set. Generated 3D models of the protein-metal coordination complexes reach root-mean-square deviation values under 1. 0 Å between calculated and experimental structures. The whole process is purely based on finding poses that satisfy metal-derived geometrical rules without needing sequence or fine electronic inputs. Additional post-optimizations, including receptor flexibility, have been tested and suggest that more extensive searches, required when the host structures present a low level of pre-organization, are also possible. With this new update, GaudiMM is now able to look for metal-binding sites in biological scaffolds and clearly shows how explicitly considering the geometric particularities of the first coordination sphere of the metal in a docking process provides excellent results.
Grants: Ministerio de Economía y Competitividad CTQ2017-87889-P
Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1323
Note: This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. License: https://pubs.acs.org/page/policy/authorchoice_termsofuse.html
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Published in: ACS omega, Vol. 4, Num. 2 (February 2019) , p. 3726-3731, ISSN 2470-1343

DOI: 10.1021/acsomega.8b03457
PMID: 31459585


6 p, 1.6 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2020-07-06, last modified 2023-09-10



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