CONICET | Buscador de Institutos y Recursos Humanos

Binding between two biomolecules requires a considerable reorganization of the solvent surrounding the contact surface. In this work, water molecules around the carbohydrate recognition domain of human galectin-1, a protein involved in the immune response, are studied using molecular dynamics simulations. In a first step, we have identified and characterized with parameters such as survival probabilities and radial and angular distribution functions the structurally and energetically relevant water molecules associated with residues responsible of the recognition of the ligand, in order to shed light on the time-scales and mechanisms of water attachment to this protein. In a second step, we have computed the contribution of water molecules to the thermodynamics properties using statistical mechanical formulas for the energy. This information was then taken into account for an analysis of the water molecules conserved in the crystallographic structure of the protein with one of its ligands, N-acetilgalactosamine. The energetic properties of the identified water sites show a good correlation with its role in the binding of the carbohydrate; as expected, water sites that are replaced by carbohydrate defined position show a free-energy profile that favors their localization in those regions. On the other hand, water sites that remain not replaced by the ligand show a less favorable free-energy profile. However, no correlation was found in the energy -Lennard-Jones and electrostatic components evaluated for those sites. From these studies, it was possible to assess that water solvation thermodynamics at the binding site may provide significant information about the ligand binding process, not easily accessible by other techniques. Results also expose difficulties encountered to interpret at microscopic scale the real contribution of enthalpy and entropy in this process.

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