Lipid systems

Modeling and simulation of cell membranes

Cell membranes are made of bilayer lipid surfactants inside an aqueous environment. Simulations of a protein in the cell membrane at all-atom level, including all sites and interactions, can involve to move 128 lipid sites of DMPC lipid molecules inside a sea of 3654 water molecules at the simplest level or considering the interaction of +200000 atomic sites for a protein inside a cell membrane. The main aim of the research developed is to significantly improve the realism of the membrane, including ionic species, cholesterol and selected proteins and, especially, to enlight the interactions of small molecuels (tryptophan, melatonin, serotonin), proteins and drugs within the membrane. The most recent developments involve the simulation of proteins KRas at cellular interfaces, simulating systems of +200000 atoms at the all-atom level and including new drugs designed in silico able to modifiy the activation of the oncogenes at the atomic level.

Lipid chain performing a flip-flop transition in a biological membrane

The study of rare events is a computational challenge due to the tiny amount of trajectories in phase space which lead to such phenomena, compared with the total amount of trajectories described by a microscopical system. A new technique named transition path sampling, which is able to analyze reactive trajectories in configurational space without preconceived information about potential energy surfaces or transition states of the system, was developed by the research group of Prof. David Chandler in the University of California at Berkeley. We have employed that technique to study the transition state structure of NaCl dissociation in water and, more recently, flip-flop transitions of lipids in biomembranes.