CELLmicrocosmos 2.2 MembraneEditor: a modular interactive shape-based software approach to solve heterogeneous membrane packing problems.

ABSTRACT

New perspectives have been developed to understand the processes of modeling heterogeneous membranes. These are crucial steps prior to applying advanced techniques like molecular dynamic simulations of whole membrane systems. Lipid, protein, and membrane packing problems are addressed based on biochemical properties in combination with computational optimization techniques. The CELLmicrocosmos 2.2 MembraneEditor (CmME) is introduced as an appropriate framework to handle such problems by offering diverse algorithmic approaches. Its algorithm plug-in-interface enables modelers to generate problem-specific algorithms. Good solutions concerning runtime and lipid density are realized by focusing on the outer shapes of the PDB-based molecules. Application cases are presented like the publication-based modeling of inner and outer mitochondrial membrane-fragments, semiautomatic incorporation of proteins, and the assembly of rafts. Concerning geometrical aspects of the lipids, the achieved results are consistent with experimental observations related to lipid densities and distributions. Finally, two membranes simulated with GROMACS are analyzed and compared the first is generated with conventional scripting techniques, the second with the CmME Distributor algorithm. The examples prove that CmME is a valuable and versatile tool for a broad set of applications in analysis and visualization of biomembranes.