INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
Coarsed-grained molecular dynamics study of the interaction between GAPDHR and small unilamellar vesicles
Autor/es:
AVILA CL; MORERO, RD; CHEHIN, RN
Lugar:
La Plata
Reunión:
Congreso; XXXVII Reunion Anual de la Sociedad Argentina de Biofisica; 2008
Resumen:
Membrane fusion is a key step in many processes such us membrane trafficking, exocitosys, fertilization and virus infection. Negatively charged phospholipid membranes do not fuse spontaneously but the process can be promoted by specific proteins that form membrane-bridging complexes and pull the fusion partners into close proximity. In addition, the proteins are believed to induce local curvature. This stress provides the energy to drive the subsequent fusion process.In previous work, the capacity of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDHR) to bind, aggregate, destabilize and fuse negatively charged vesicles, has been demonstrated. Using an electrostatic analysis based on the Poisson-Boltzmann model, we proposed that a positively charged concave surface on GAPDHR might be involved in the plastering and destabilization of the negatively charged vesicle membrane.The molecular structures and transition stages cannot be visualized experimentally with the techniques currently available. In this way, molecular modelling techniques, such us molecular dynamics (MD) simulations, provides valuable tools to study the fusion process at the nanoscale in detail. As simulating the complete fusion pathway is computationally unfeasible using fully atomistic MD, we used instead a coarse-grained approach developed by Marrink et al. Initially developed for simulation of lipids and surfactants, this coarse-grained model accurately reproduces structural and dynamic properties of lipids as well as lipid phase transitions. Recently an extension of this force field has been presented to model peptides and proteins, enabling simulations of protein systems in the presence of lipids and surfactants at a coarse-grained level.In this work, we explore the dynamics of the protein membrane interactions between GAPDHR and a mixed DOPC:DOPA small unilamelar vesicles using coarse-grained MD on a microsecond time scale.