Exploring asymmetry in the galactosil binding homodimeric protein Galectin-1

ROMERO, JUAN MANUEL; ESTRIN, DARÍO ARIEL; RABINOVICH, GABRIEL ADRIÁN; DI LELLA, SANTIAGO

San Javier, Tucumán

Congreso; XLI Reunión Anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofísica

Galectin-1 is a β-galatoside-binding protein involved in cell communication and differentiation processes. It consists of a 134-aminoacid domain which has been proved to exist as a homodimer at physiological conditions. Despite symmetry is usually the rule in homodimers, in a previous investigation we showed that temporal asymmetries between chemically identical subunits can lead to structural and dynamic differences. In this work, we conducted 100 ns molecular dynamics simulations of a number of Galectin-1 systems in different states and bound conditions, followed by an energetic and structural analysis in order to explore lactose binding processes in each monomer. The methods used were the widely known MM-GBSA, as a classical approximation, and the recently developed QM-MM/COSMO, that implements a semi-empirical Hamiltonian for energy calculations. According to our expectations, there was a difference betweenthe monomers lactose-binding energy, which seemed to be slightlydependent of the other monomer's state. As regards entropy, ligand binding had a different impact on each monomer's flexibility and conformational sampling. Although these conclusions are only valid for the timescale explored during the simulation, the implications of our results could be of interest for the biological and physiological implications of this multifunctional galectin.