Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy
Formation of protein ligand complexes is a fundamental phenomenon in biochemistry. During the process, significant solvent reorganization is produced along the contact surface and many water molecules strongly bound to the protein's ligand binding site must be displaced. Both the thermodynamics...
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2009
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paper:paper_15206106_v113_n25_p8717_Gauto2023-06-08T16:19:01Z Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy Gauto, Diego Fernando Guardia, Carlos Manuel Alberto Estrin, Dario Ariel Martí, Marcelo Adrián Binding energy Binding sites Biochemistry Carbohydrates Complexation Dynamics Functional groups Ligands Molecular dynamics Molecules Probability density function Proteins Solvation Solvents Statistical mechanics Thermodynamic properties Analysis tools Associated water Binding free energy Binding proteins Bulk density Carbohydrate binding Carbohydrate recognition Carbohydrate-recognition domains Contact surface Cyclophilin Explicit water Galectin-1 Hydroxyl groups Ligand binding Ligand structure Ligand-binding sites MD simulation Microscopic levels Molecular dynamics simulations Multi-modular Protein affinity Protein surface Protein-ligand complexes Recognition process Sialidase Solvation structure Solvent environments Solvent reorganization Thermodynamics and kinetics Water molecule Water analysis Formation of protein ligand complexes is a fundamental phenomenon in biochemistry. During the process, significant solvent reorganization is produced along the contact surface and many water molecules strongly bound to the protein's ligand binding site must be displaced. Both the thermodynamics and kinetics of this process are complex and a clear understanding at the microscopic level has been not achieved so far. Special attention has been paid to the structure of water molecules on carbohydrate recognition sites of various proteins, and many studies support the idea that displacement of these water molecules should have a crucial effect on the binding free energy. Molecular dynamics (MD) simulations in explicit water solvent is a very promising approach for this type of studies. Using MD simulations combined with statistical mechanics analysis, thermodynamic properties of these water molecules can be computed and analyzed in a comparative view. Using this idea, we developed a set of analysis tools to link solvation with ligand binding in a key carbohydrate binding protein, human galectin-1 (hGal-1). Specifically, we defined water sites (WS) in terms of the thermodynamic properties of water molecules strongly bound to protein surfaces. In the present work, we selected a group of proteins whose ligand bound complexes have been already structurally characterized in order to extend the analysis of the role of the surface associated water molecules in the ligand binding and recognition process. The selected proteins are concanavalin-A (Con-A), galectin-3 (Gal-3), cyclophilin-A (Cyp-A), and two modules CBM40 and CBM32 of the multimodular bacterial sialidase. Our results show that the probability of finding water molecules inside the WS, p(V), with respect to the bulk density is directly correlated to the likeliness of finding an hydroxyl group of the ligand in the protein-ligand complex. This information can be used to analyze in detail the solvation structure of the carbohydrate recognition domain (CRD) and its relation to the possible protein ligand complexes and suggests addition of OH-containing functional groups to displace water from high p(V) WS to enhance drugs, specially glycomimetic-drugs, protein affinity, and/or specificity. © 2009 American Chemical Society. Fil:Gauto, D.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Guardia, C.M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.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. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v113_n25_p8717_Gauto http://hdl.handle.net/20.500.12110/paper_15206106_v113_n25_p8717_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 |
Binding energy Binding sites Biochemistry Carbohydrates Complexation Dynamics Functional groups Ligands Molecular dynamics Molecules Probability density function Proteins Solvation Solvents Statistical mechanics Thermodynamic properties Analysis tools Associated water Binding free energy Binding proteins Bulk density Carbohydrate binding Carbohydrate recognition Carbohydrate-recognition domains Contact surface Cyclophilin Explicit water Galectin-1 Hydroxyl groups Ligand binding Ligand structure Ligand-binding sites MD simulation Microscopic levels Molecular dynamics simulations Multi-modular Protein affinity Protein surface Protein-ligand complexes Recognition process Sialidase Solvation structure Solvent environments Solvent reorganization Thermodynamics and kinetics Water molecule Water analysis |
| spellingShingle |
Binding energy Binding sites Biochemistry Carbohydrates Complexation Dynamics Functional groups Ligands Molecular dynamics Molecules Probability density function Proteins Solvation Solvents Statistical mechanics Thermodynamic properties Analysis tools Associated water Binding free energy Binding proteins Bulk density Carbohydrate binding Carbohydrate recognition Carbohydrate-recognition domains Contact surface Cyclophilin Explicit water Galectin-1 Hydroxyl groups Ligand binding Ligand structure Ligand-binding sites MD simulation Microscopic levels Molecular dynamics simulations Multi-modular Protein affinity Protein surface Protein-ligand complexes Recognition process Sialidase Solvation structure Solvent environments Solvent reorganization Thermodynamics and kinetics Water molecule Water analysis Gauto, Diego Fernando Guardia, Carlos Manuel Alberto Estrin, Dario Ariel Martí, Marcelo Adrián Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy |
| topic_facet |
Binding energy Binding sites Biochemistry Carbohydrates Complexation Dynamics Functional groups Ligands Molecular dynamics Molecules Probability density function Proteins Solvation Solvents Statistical mechanics Thermodynamic properties Analysis tools Associated water Binding free energy Binding proteins Bulk density Carbohydrate binding Carbohydrate recognition Carbohydrate-recognition domains Contact surface Cyclophilin Explicit water Galectin-1 Hydroxyl groups Ligand binding Ligand structure Ligand-binding sites MD simulation Microscopic levels Molecular dynamics simulations Multi-modular Protein affinity Protein surface Protein-ligand complexes Recognition process Sialidase Solvation structure Solvent environments Solvent reorganization Thermodynamics and kinetics Water molecule Water analysis |
| description |
Formation of protein ligand complexes is a fundamental phenomenon in biochemistry. During the process, significant solvent reorganization is produced along the contact surface and many water molecules strongly bound to the protein's ligand binding site must be displaced. Both the thermodynamics and kinetics of this process are complex and a clear understanding at the microscopic level has been not achieved so far. Special attention has been paid to the structure of water molecules on carbohydrate recognition sites of various proteins, and many studies support the idea that displacement of these water molecules should have a crucial effect on the binding free energy. Molecular dynamics (MD) simulations in explicit water solvent is a very promising approach for this type of studies. Using MD simulations combined with statistical mechanics analysis, thermodynamic properties of these water molecules can be computed and analyzed in a comparative view. Using this idea, we developed a set of analysis tools to link solvation with ligand binding in a key carbohydrate binding protein, human galectin-1 (hGal-1). Specifically, we defined water sites (WS) in terms of the thermodynamic properties of water molecules strongly bound to protein surfaces. In the present work, we selected a group of proteins whose ligand bound complexes have been already structurally characterized in order to extend the analysis of the role of the surface associated water molecules in the ligand binding and recognition process. The selected proteins are concanavalin-A (Con-A), galectin-3 (Gal-3), cyclophilin-A (Cyp-A), and two modules CBM40 and CBM32 of the multimodular bacterial sialidase. Our results show that the probability of finding water molecules inside the WS, p(V), with respect to the bulk density is directly correlated to the likeliness of finding an hydroxyl group of the ligand in the protein-ligand complex. This information can be used to analyze in detail the solvation structure of the carbohydrate recognition domain (CRD) and its relation to the possible protein ligand complexes and suggests addition of OH-containing functional groups to displace water from high p(V) WS to enhance drugs, specially glycomimetic-drugs, protein affinity, and/or specificity. © 2009 American Chemical Society. |
| author |
Gauto, Diego Fernando Guardia, Carlos Manuel Alberto Estrin, Dario Ariel Martí, Marcelo Adrián |
| author_facet |
Gauto, Diego Fernando Guardia, Carlos Manuel Alberto Estrin, Dario Ariel Martí, Marcelo Adrián |
| author_sort |
Gauto, Diego Fernando |
| title |
Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy |
| title_short |
Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy |
| title_full |
Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy |
| title_fullStr |
Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy |
| title_full_unstemmed |
Carbohydrate-binding proteins: Dissecting ligand structures through solvent environment occupancy |
| title_sort |
carbohydrate-binding proteins: dissecting ligand structures through solvent environment occupancy |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v113_n25_p8717_Gauto http://hdl.handle.net/20.500.12110/paper_15206106_v113_n25_p8717_Gauto |
| work_keys_str_mv |
AT gautodiegofernando carbohydratebindingproteinsdissectingligandstructuresthroughsolventenvironmentoccupancy AT guardiacarlosmanuelalberto carbohydratebindingproteinsdissectingligandstructuresthroughsolventenvironmentoccupancy AT estrindarioariel carbohydratebindingproteinsdissectingligandstructuresthroughsolventenvironmentoccupancy AT martimarceloadrian carbohydratebindingproteinsdissectingligandstructuresthroughsolventenvironmentoccupancy |
| _version_ |
1768544055353933824 |