INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Solvent occupancy analysis in ligand structure prediction: the case of Galectin-1
DI LELLA, SANTIAGO; MARTÍ, MARCELO ADRIÁN; ESTRIN, DARÍO ARIEL
Congreso; 7th EBSA European Biophysics Congress; 2009
European Biophysical Societies Association
Formation of protein ligand complexes is a fundamental phe-nomenum in biochemistry. During the process, significantsolvent reorganization is produced along the contact surface.Using MD simulations in explicit solvent combined with sta-tistical mechanics analysis, thermodynamic properties of wa-ter molecules around proteins can be computed and analyzedin a comparative view. Based on this idea, we developed aset of analysis tools to link solvation with ligand binding in akey carbohydrate binding protein, human galectin-1 (hGal-1). Specifically, we defined water sites (WS) in terms ofthe thermodynamic properties of water molecules stronglybound to protein surfaces. We then succesfully extended theanalysis of the role of the surface associated water moleculesin the ligand binding and recognition process to many othercarbohydrate binding proteins.Our results show that the probability of finding watermolecules inside the WS, p(v), with respect to the bulkdensity is directly correlated to the likeliness of finding anoxhydril group of the ligand in the protein-ligand complex.This information can be used to predict possible complexstructures when unavailable, and suggest addition of OH-containing functional groups to displace water from high p(v)WS to enhance drug, specially glycomimetic-drugs, proteinaffinity and/or specificity.