title: Mesoscopic simulation of phospholipid membranes, peptides, and proteins with molecular fragment dynamics.
abstract: Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connected by harmonic springs to represent larger molecular entities in order to maintain a comparatively accurate representation of covalent bonding and molecular characteristics. For this study the MFD approach is extended to accomplish long-term simulations (up to the microsecond scale) of large molecular ensembles (representing millions of atoms) containing phospholipid membranes, peptides, and proteins. For peptides and proteins a generally applicable fragmentation scheme is introduced in combination with specific backbone forces that keep native spatial shapes with adequate levels of flexibility or rigidity. The new approach is demonstrated by MFD simulations of the formation and characteristics of phospholipid membranes and vesicles, vesicle-membrane fusion, the backbone force dependency of the overall structural flexibility of dumbbell-shaped Calmodulin, the stability of subunit-aggregation of tetrameric hemoglobin, and the collaborative interaction of Kalata B1 cyclotides with a phospholipid membrane. All findings are in reasonable agreement with experimental as well as alternative simulation results. Thus, the extended MFD approach may become a new tool for biomolecular system studies to allow for comparatively fast simulative investigations in combination with a comparatively high chemical granularity.
authors.affiliation: †Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, 45141 Essen, Germany.|‡Institute for Bioinformatics and Cheminformatics, Westphalian University of Applied Sciences, 45665 Recklinghausen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Truszkowski
authors.affiliation: ⊥Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians University Munich, 80539 Munich, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: van den Broek
authors.affiliation: †Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, 45141 Essen, Germany.|§CAM-D Technologies, 45127 Essen, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kuhn
authors.affiliation: ‡Institute for Bioinformatics and Cheminformatics, Westphalian University of Applied Sciences, 45665 Recklinghausen, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Zielesny
authors.affiliation: †Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, 45141 Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Epple
mesh_terms: D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D047169:Cyclotides / Q000737:chemistry / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D055550:Protein Stability; D017433:Protein Structure, Secondary
chemical_list: D002147:Calmodulin; D047169:Cyclotides; D006454:Hemoglobins; D008051:Lipid Bilayers; C091930:kalata B1; D004134:Dimyristoylphosphatidylcholine