SYSTEMATIC COARSE-GRAINING OF LIPID BILAYERS WITH IMPLICIT SOLVENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lipid bilayers are one of the key structural components of all living cells. They compartmentalize and organize the cellular biochemical environment into organelles and play a key role in mediating controlled transport of substances and signals between spatially separated domains. Rather than merely solubilizing membrane proteins, as has long been believed, we now know that lipid bilayers actively participate in many of these cellular events, and this has generated a renewed interest in their biophysical and material characteristics. However, many of the events on which current research focuses -- vesiculation, sorting, endocytosis, sensing, locomotion, etc. -- occur on length- and associated time-scales which are significantly beyond the reach of atomistic molecular simulation techniques. Hence, much interest has been devoted to the development of coarse-grained models that reduce the number of required degrees of freedom and enable the systematic studies of phenomena which are largely independent of chemical detail [1]. Among them, models that eliminate the need for an embedding solvent hold the largest promise to finally bridge the gap to the organelle level [2], but they are still a very recent addition to the simulation toolbox and require further studies. The PI has recently developed a highly coarse-grained solvent-free lipid model [3] and successfully applied it to problems involving composition-curvature coupling [4] and curvature-mediated interactions [5]. While robustly representing large-scale membrane properties, it is not finely enough resolved to account for structural bilayer detail that matters for several aspects of lipid-protein interactions. In order to bridge the gap backwards to more detailed descriptions of lipids, the PI proposes to carefully reintroduce degrees of freedom and lipid species individuality, while at the same time keeping the embedding solvent implicit. The plan is to follow a structure-based coarse- (or fine-) graining technique which links existing atomistic and mesoscopic scales to the solvent free realm. Such an approach will in particular require significant computational power to obtain very good structural statistics on the finer levels of detail, thus necessitating the access to supercomputing facilities. The CPU time awarded within the framework of a DAC will both serve as an initial system startup and -- more importantly -- help to gain crucial experience and scaling information required to formulate a subsequent MRAC proposal. [1] M. Muller, K. Katsov, and M. Schick, "Biological and synthetic membranes: What can be learned from a coarse-grained description?", Phys. Rep. _434_, 113 (2006); M. Venturoli, M.M. Sperotto, M. Kranenburg, and B. Smit, "Mesoscopic models of biological membranes", Phys. Rep. _437_, 1 (2006). [2] G. Brannigan, L.C.L. Lin, and F.L.H Brown, "Implicit solvent simulation models for biomembranes", Eur. Biophys. J. _35_, 104 (2006). [3] I.R. Cooke, K. Kremer, and M. Deserno, "Tunable generic model for fluid bilayer membranes", Phys. Rev. E _72_, 011506 (2005); I.R. Cooke and M. Deserno, "Solvent-free model for self-assembling fluid bilayer membranes: Stabilization of the fluid phase based on broad attractive tail potentials", J. Chem. Phys. _123_, 224710 (2005). [4] I.R. Cooke and M. Deserno, "Coupling between lipid shape and membrane curvature", Biophys. J. _91_, 487 (2006). [5] B.J. Reynwar, G. Illya, V.A. Harmandaris, M.M. Muller, K. Kremer, and M. Deserno, "Aggregation and vesiculation of membrane proteins by curvature-mediated interactions", Nature _447_, 461-464 (2007).