Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures
Understanding protein-ligand interactions is a fundamental question in basic biochemistry, and the role played by the solvent along this process is not yet fully understood. This fact is particularly relevant in lectins, proteins that mediate a large variety of biological processes through the recog...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_09596658_v25_n2_p181_Modenutti |
| Aporte de: |
| id |
todo:paper_09596658_v25_n2_p181_Modenutti |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_09596658_v25_n2_p181_Modenutti2023-10-03T15:53:07Z Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures Modenutti, C. Gauto, D. Radusky, L. Blanco, J. Turjanski, A. Hajos, S. Marti, M.A. carbohydrate docking hydration lectin Naive Bayes classifier sites water sites carbohydrate lectin oxygen water disaccharide lectin monosaccharide protein binding trisaccharide water accuracy amino acid composition Article Bayesian learning binding site carbohydrate analysis crystal structure crystallography hydrogen bond ligand binding molecular docking molecular recognition predictive value priority journal protein analysis protein interaction protein structure Bayes theorem chemical structure chemistry conformation X ray crystallography Bayes Theorem Binding Sites Carbohydrate Conformation Crystallography, X-Ray Disaccharides Lectins Models, Molecular Monosaccharides Protein Binding Trisaccharides Water Understanding protein-ligand interactions is a fundamental question in basic biochemistry, and the role played by the solvent along this process is not yet fully understood. This fact is particularly relevant in lectins, proteins that mediate a large variety of biological processes through the recognition of specific carbohydrates. In the present work, we have thoroughly analyzed a nonredundant and well-curated set of lectin structures looking for a potential relationship between the structural water properties in the apo-structures and the corresponding protein-ligand complex structures. Our results show that solvent structure adjacent to the binding sites mimics the ligand oxygen structural framework in the resulting protein-ligand complex, allowing us to develop a predictive method using a Naive Bayes classifier. We also show how these properties can be used to improve docking predictions of lectin-carbohydrate complex structures in terms of both accuracy and precision, thus developing a solid strategy for the rational design of glycomimetic drugs. Overall our results not only contribute to the understanding of protein-ligand complexes, but also underscore the role of the water solvent in the ligand recognition process. Finally, we discuss our findings in the context of lectin specificity and ligand recognition properties. © 2014 The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Fil:Gauto, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Turjanski, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09596658_v25_n2_p181_Modenutti |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
carbohydrate docking hydration lectin Naive Bayes classifier sites water sites carbohydrate lectin oxygen water disaccharide lectin monosaccharide protein binding trisaccharide water accuracy amino acid composition Article Bayesian learning binding site carbohydrate analysis crystal structure crystallography hydrogen bond ligand binding molecular docking molecular recognition predictive value priority journal protein analysis protein interaction protein structure Bayes theorem chemical structure chemistry conformation X ray crystallography Bayes Theorem Binding Sites Carbohydrate Conformation Crystallography, X-Ray Disaccharides Lectins Models, Molecular Monosaccharides Protein Binding Trisaccharides Water |
| spellingShingle |
carbohydrate docking hydration lectin Naive Bayes classifier sites water sites carbohydrate lectin oxygen water disaccharide lectin monosaccharide protein binding trisaccharide water accuracy amino acid composition Article Bayesian learning binding site carbohydrate analysis crystal structure crystallography hydrogen bond ligand binding molecular docking molecular recognition predictive value priority journal protein analysis protein interaction protein structure Bayes theorem chemical structure chemistry conformation X ray crystallography Bayes Theorem Binding Sites Carbohydrate Conformation Crystallography, X-Ray Disaccharides Lectins Models, Molecular Monosaccharides Protein Binding Trisaccharides Water Modenutti, C. Gauto, D. Radusky, L. Blanco, J. Turjanski, A. Hajos, S. Marti, M.A. Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| topic_facet |
carbohydrate docking hydration lectin Naive Bayes classifier sites water sites carbohydrate lectin oxygen water disaccharide lectin monosaccharide protein binding trisaccharide water accuracy amino acid composition Article Bayesian learning binding site carbohydrate analysis crystal structure crystallography hydrogen bond ligand binding molecular docking molecular recognition predictive value priority journal protein analysis protein interaction protein structure Bayes theorem chemical structure chemistry conformation X ray crystallography Bayes Theorem Binding Sites Carbohydrate Conformation Crystallography, X-Ray Disaccharides Lectins Models, Molecular Monosaccharides Protein Binding Trisaccharides Water |
| description |
Understanding protein-ligand interactions is a fundamental question in basic biochemistry, and the role played by the solvent along this process is not yet fully understood. This fact is particularly relevant in lectins, proteins that mediate a large variety of biological processes through the recognition of specific carbohydrates. In the present work, we have thoroughly analyzed a nonredundant and well-curated set of lectin structures looking for a potential relationship between the structural water properties in the apo-structures and the corresponding protein-ligand complex structures. Our results show that solvent structure adjacent to the binding sites mimics the ligand oxygen structural framework in the resulting protein-ligand complex, allowing us to develop a predictive method using a Naive Bayes classifier. We also show how these properties can be used to improve docking predictions of lectin-carbohydrate complex structures in terms of both accuracy and precision, thus developing a solid strategy for the rational design of glycomimetic drugs. Overall our results not only contribute to the understanding of protein-ligand complexes, but also underscore the role of the water solvent in the ligand recognition process. Finally, we discuss our findings in the context of lectin specificity and ligand recognition properties. © 2014 The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
| format |
JOUR |
| author |
Modenutti, C. Gauto, D. Radusky, L. Blanco, J. Turjanski, A. Hajos, S. Marti, M.A. |
| author_facet |
Modenutti, C. Gauto, D. Radusky, L. Blanco, J. Turjanski, A. Hajos, S. Marti, M.A. |
| author_sort |
Modenutti, C. |
| title |
Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| title_short |
Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| title_full |
Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| title_fullStr |
Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| title_full_unstemmed |
Using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| title_sort |
using crystallographic water properties for the analysis and prediction of lectin-carbohydrate complex structures |
| url |
http://hdl.handle.net/20.500.12110/paper_09596658_v25_n2_p181_Modenutti |
| work_keys_str_mv |
AT modenuttic usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures AT gautod usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures AT raduskyl usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures AT blancoj usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures AT turjanskia usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures AT hajoss usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures AT martima usingcrystallographicwaterpropertiesfortheanalysisandpredictionoflectincarbohydratecomplexstructures |
| _version_ |
1807315469966770176 |