Solvent structure improves docking prediction in lectin-carbohydrate complexes
Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico...
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2013
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paper:paper_09596658_v23_n2_p241_Gauto2023-06-08T15:57:04Z Solvent structure improves docking prediction in lectin-carbohydrate complexes Gauto, Diego Fernando Petruk, Ariel Alcides Martí, Marcelo Adrián AutoDock4 carbohydrate complex docking galectins hydration site lectin proteins saccharide solvent structure water site carbohydrate lectin monosaccharide solvent tetrasaccharide article chemical modification chemical structure complex formation computer program molecular docking molecular dynamics prediction priority journal protein carbohydrate interaction simulation surface property Binding Sites Carbohydrates Galectins Ligands Molecular Docking Simulation Molecular Dynamics Simulation Protein Binding Protein Conformation Protein Structure, Tertiary Proteins Software Solvents Water Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico docking methods have a long-standing tradition in predicting protein-ligand complexes, and allow a potentially fast exploration of a number of possible protein-carbohydrate complex structures. However, determining which of these predicted complexes represents the correct structure is not always straightforward.In this work, we present a modification of the scoring function provided by AutoDock4, a widely used docking software, on the basis of analysis of the solvent structure adjacent to the protein surface, as derived from molecular dynamics simulations, that allows the definition and characterization of regions with higher water occupancy than the bulk solvent, called water sites. They mimic the interaction held between the carbohydrate-OH groups and the protein. We used this information for an improved docking method in relation to its capacity to correctly predict the protein-carbohydrate complexes for a number of tested proteins, whose ligands range in size from mono-to tetrasaccharide. Our results show that the presented method significantly improves the docking predictions. The resulting solvent-structure-biased docking protocol, therefore, appears as a powerful tool for the design and optimization of development of glycomimetic drugs, while providing new insights into protein-carbohydrate interactions. Moreover, the achieved improvement also underscores the relevance of the solvent structure to the protein carbohydrate recognition process. © 2012 The Author. Fil:Gauto, D.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Petruk, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martí, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v23_n2_p241_Gauto http://hdl.handle.net/20.500.12110/paper_09596658_v23_n2_p241_Gauto |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
AutoDock4 carbohydrate complex docking galectins hydration site lectin proteins saccharide solvent structure water site carbohydrate lectin monosaccharide solvent tetrasaccharide article chemical modification chemical structure complex formation computer program molecular docking molecular dynamics prediction priority journal protein carbohydrate interaction simulation surface property Binding Sites Carbohydrates Galectins Ligands Molecular Docking Simulation Molecular Dynamics Simulation Protein Binding Protein Conformation Protein Structure, Tertiary Proteins Software Solvents Water |
| spellingShingle |
AutoDock4 carbohydrate complex docking galectins hydration site lectin proteins saccharide solvent structure water site carbohydrate lectin monosaccharide solvent tetrasaccharide article chemical modification chemical structure complex formation computer program molecular docking molecular dynamics prediction priority journal protein carbohydrate interaction simulation surface property Binding Sites Carbohydrates Galectins Ligands Molecular Docking Simulation Molecular Dynamics Simulation Protein Binding Protein Conformation Protein Structure, Tertiary Proteins Software Solvents Water Gauto, Diego Fernando Petruk, Ariel Alcides Martí, Marcelo Adrián Solvent structure improves docking prediction in lectin-carbohydrate complexes |
| topic_facet |
AutoDock4 carbohydrate complex docking galectins hydration site lectin proteins saccharide solvent structure water site carbohydrate lectin monosaccharide solvent tetrasaccharide article chemical modification chemical structure complex formation computer program molecular docking molecular dynamics prediction priority journal protein carbohydrate interaction simulation surface property Binding Sites Carbohydrates Galectins Ligands Molecular Docking Simulation Molecular Dynamics Simulation Protein Binding Protein Conformation Protein Structure, Tertiary Proteins Software Solvents Water |
| description |
Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico docking methods have a long-standing tradition in predicting protein-ligand complexes, and allow a potentially fast exploration of a number of possible protein-carbohydrate complex structures. However, determining which of these predicted complexes represents the correct structure is not always straightforward.In this work, we present a modification of the scoring function provided by AutoDock4, a widely used docking software, on the basis of analysis of the solvent structure adjacent to the protein surface, as derived from molecular dynamics simulations, that allows the definition and characterization of regions with higher water occupancy than the bulk solvent, called water sites. They mimic the interaction held between the carbohydrate-OH groups and the protein. We used this information for an improved docking method in relation to its capacity to correctly predict the protein-carbohydrate complexes for a number of tested proteins, whose ligands range in size from mono-to tetrasaccharide. Our results show that the presented method significantly improves the docking predictions. The resulting solvent-structure-biased docking protocol, therefore, appears as a powerful tool for the design and optimization of development of glycomimetic drugs, while providing new insights into protein-carbohydrate interactions. Moreover, the achieved improvement also underscores the relevance of the solvent structure to the protein carbohydrate recognition process. © 2012 The Author. |
| author |
Gauto, Diego Fernando Petruk, Ariel Alcides Martí, Marcelo Adrián |
| author_facet |
Gauto, Diego Fernando Petruk, Ariel Alcides Martí, Marcelo Adrián |
| author_sort |
Gauto, Diego Fernando |
| title |
Solvent structure improves docking prediction in lectin-carbohydrate complexes |
| title_short |
Solvent structure improves docking prediction in lectin-carbohydrate complexes |
| title_full |
Solvent structure improves docking prediction in lectin-carbohydrate complexes |
| title_fullStr |
Solvent structure improves docking prediction in lectin-carbohydrate complexes |
| title_full_unstemmed |
Solvent structure improves docking prediction in lectin-carbohydrate complexes |
| title_sort |
solvent structure improves docking prediction in lectin-carbohydrate complexes |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09596658_v23_n2_p241_Gauto http://hdl.handle.net/20.500.12110/paper_09596658_v23_n2_p241_Gauto |
| work_keys_str_mv |
AT gautodiegofernando solventstructureimprovesdockingpredictioninlectincarbohydratecomplexes AT petrukarielalcides solventstructureimprovesdockingpredictioninlectincarbohydratecomplexes AT martimarceloadrian solventstructureimprovesdockingpredictioninlectincarbohydratecomplexes |
| _version_ |
1768543431033880576 |