Carbohydrate-binding proteins: Dissecting ligand structures trough solvent enviroment occupancy

DIEGO F. GAUTO, SANTIAGO DI LELLA, CARLOS M. A. GUARDIA, DARıO A. ESTRIN, H. MONACO AND MARCELO A. MARTı

Buzios. Brasil. Hotel Atlantico Buzios

Congreso; VII Congreso Iberoamericano de Biofisica; 2009

Sociedad Argentina de Biofisica

<!-- @page { size: 21cm 29.7cm; margin: 2cm } P { margin-bottom: 0.21cm } --> Objectives During the process of protein ligand complexes formation, 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. Using MD simulations combined with statistical mechanics analysis, thermodynamic properties of water molecules tightly associated to the surfaces of carbohydrate recognition sites (CRD) may be computed and analyzed, yielding valuable information concerning ligand binding and discrimination mechanism. Methods To study this relation systematically, we defined so called water sites (WS) represented by spatial zones in the protein surface, displaying high water finding probability when compared with the bulk solution. Based on this definition we computed several structural and dynamical parameters of each WS in number of carbohydrate binding proteins, namely concanavalin-A, galectin-3, cyclophilin-A, and two modules CBM40 and CBM32 of the multimodular bacterial sialidas. Results 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. Conclusion 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.