GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm
Protein−ligand docking is a widely used method to generate solutions for the binding of a small molecule with its target in a short amount of time. However, these methods provide identification of physically sound protein−ligand complexes without a complete view of the binding pr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/13/3155 |
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| author | José-Emilio Sánchez-Aparicio Giuseppe Sciortino Daniel Viladrich Herrmannsdoerfer Pablo Orenes Chueca Jaime Rodríguez-Guerra Pedregal Jean-Didier Maréchal |
| author_facet | José-Emilio Sánchez-Aparicio Giuseppe Sciortino Daniel Viladrich Herrmannsdoerfer Pablo Orenes Chueca Jaime Rodríguez-Guerra Pedregal Jean-Didier Maréchal |
| author_sort | José-Emilio Sánchez-Aparicio |
| collection | DOAJ |
| description | Protein−ligand docking is a widely used method to generate solutions for the binding of a small molecule with its target in a short amount of time. However, these methods provide identification of physically sound protein−ligand complexes without a complete view of the binding process dynamics, which has been recognized to be a major discriminant in binding affinity and ligand selectivity. In this paper, a novel piece of open-source software to approach this problem is presented, called GPathFinder. It is built as an extension of the modular GaudiMM platform and is able to simulate ligand diffusion pathways at atomistic level. The method has been benchmarked on a set of 20 systems whose ligand-binding routes were studied by other computational tools or suggested from experimental “snapshots”. In all of this set, GPathFinder identifies those channels that were already reported in the literature. Interestingly, the low-energy pathways in some cases indicate novel possible binding routes. To show the usefulness of GPathFinder, the analysis of three case systems is reported. We believe that GPathFinder is a software solution with a good balance between accuracy and computational cost, and represents a step forward in extending protein−ligand docking capacities, with implications in several fields such as drug or enzyme design. |
| first_indexed | 2024-04-12T02:39:34Z |
| format | Article |
| id | doaj.art-3d4b682d430a4ec1a26f3f4a53425780 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T02:39:34Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3d4b682d430a4ec1a26f3f4a534257802022-12-22T03:51:21ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-06-012013315510.3390/ijms20133155ijms20133155GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic AlgorithmJosé-Emilio Sánchez-Aparicio0Giuseppe Sciortino1Daniel Viladrich Herrmannsdoerfer2Pablo Orenes Chueca3Jaime Rodríguez-Guerra Pedregal4Jean-Didier Maréchal5Departament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, SpainDepartament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, SpainDepartament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, SpainDepartament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, SpainDepartament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, SpainDepartament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, SpainProtein−ligand docking is a widely used method to generate solutions for the binding of a small molecule with its target in a short amount of time. However, these methods provide identification of physically sound protein−ligand complexes without a complete view of the binding process dynamics, which has been recognized to be a major discriminant in binding affinity and ligand selectivity. In this paper, a novel piece of open-source software to approach this problem is presented, called GPathFinder. It is built as an extension of the modular GaudiMM platform and is able to simulate ligand diffusion pathways at atomistic level. The method has been benchmarked on a set of 20 systems whose ligand-binding routes were studied by other computational tools or suggested from experimental “snapshots”. In all of this set, GPathFinder identifies those channels that were already reported in the literature. Interestingly, the low-energy pathways in some cases indicate novel possible binding routes. To show the usefulness of GPathFinder, the analysis of three case systems is reported. We believe that GPathFinder is a software solution with a good balance between accuracy and computational cost, and represents a step forward in extending protein−ligand docking capacities, with implications in several fields such as drug or enzyme design.https://www.mdpi.com/1422-0067/20/13/3155multi-objective genetic algorithmmolecular modelingligand diffusioncomputational chemistrymolecular dockingdrug design |
| spellingShingle | José-Emilio Sánchez-Aparicio Giuseppe Sciortino Daniel Viladrich Herrmannsdoerfer Pablo Orenes Chueca Jaime Rodríguez-Guerra Pedregal Jean-Didier Maréchal GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm International Journal of Molecular Sciences multi-objective genetic algorithm molecular modeling ligand diffusion computational chemistry molecular docking drug design |
| title | GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm |
| title_full | GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm |
| title_fullStr | GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm |
| title_full_unstemmed | GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm |
| title_short | GPathFinder: Identification of Ligand-Binding Pathways by a Multi-Objective Genetic Algorithm |
| title_sort | gpathfinder identification of ligand binding pathways by a multi objective genetic algorithm |
| topic | multi-objective genetic algorithm molecular modeling ligand diffusion computational chemistry molecular docking drug design |
| url | https://www.mdpi.com/1422-0067/20/13/3155 |
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