Replacing explicit water and lipids by implicit representation in molecular dynamics simulations

Poster (2012, September 11)

Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are ... [more ▼]

Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are not accessible by experimental methods(Lindahl, 2008). By now, many biologically relevant processes for drug design, toxicological studies and other fields of application, can not be performed by atomistic MD simulations (Lindahl, 2008). <br />In MD, the necessary time effort for carrying out a simulation is considerable and depends mainly on (1) the complexity of the simulated system (2) the simulated time scale (3) the simulation method (4) the efficiency of used hardware and software algorithms. Carried out MD simulations nowadays may still take weeks of calculation on high end computers. <br /> <br />In practice, biologically relevant processes, as e.g. protein folding, take usually place above the time scale of milli seconds. They can take up to the order of some thousands of seconds (in case of the folding of membrane proteins). Molecular dynamics computer simulations have reached the scale of micro seconds for simulations of systems where each atom was described and simulated over time.(Lindahl, 2008) <br /> <br />Nevertheless, MD has risen to an important promoter methodology for many different fields of application. By replacing bunches of atoms by artificial particles, complexity of the systems can be reduced. This method is called the coarse grain method (CG). Biggin and Bond (2008) found an acceleration of their simulation processes for self assembling membrane / protein systems in water by factor 100. They estimated one to two days of calculation for a simulated time scale of 0.1 to 0.2 micro seconds for their systems. <br /> <br />Implicit force fields like "IMPALA", aim to describe water and/or membrane molecules in simulations by a couple of simple and partially precalculable equations. “IMPALA” is a force field initially developed by our laboratory. Using this method, thousands of water and lipid molecules can be replaced, leading to a reduced complexity of the system to be simulated. <br />"IMPALA"(Ducarme et al., 1998) based on the assumption of rigid peptides and aimed to find the insertion characteristics of such in membranes. Elimination of the necessity for simulating the aqueous and lipid phase atom by atom in the software package "Gromacs"(Berendsen et al., 1995) will permit both: a gain of speed, as it was already the case for the introduction of the coarse grain method, and a gain of precision by turning rigid molecules flexible through "Gromacs". Our current work is the integration of the "IMPALA" implicit force field into "Gromacs". <br /> <br />Biggin, P.C. & Bond, P.J. Molecular dynamics simulations of membrane proteins. Methods Mol. Biol. 443, 147-60(2008). <br />Berendsen, et al. (1995) Comp. Phys. Comm. 91: 43-56. <br />Ducarme, P., Rahman, M. & Brasseur, R. IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies. Proteins 30, 357-71(1998). <br />Lindahl, E.R. (2008). Molecular dynamics simulations. Methods Mol. Biol. 443, 3-23. [less ▲]

Replacing explicit water and membrane molecules in molecular dynamics simulation to boost simulation speed

Poster (2012, February 10)

Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are ... [more ▼]

Molecular dynamics (MD) is an appropriate method for investigation of biomolecular systems and helps in explaining results from wet lab experiments or in getting further insight into details, which are not accessible by experimental methods(Lindahl, 2008). By now, many biologically relevant processes for drug design, toxicological studies and other fields of application, can not be performed by atomistic MD simulations (Lindahl, 2008). In MD, the necessary time effort for carrying out a simulation is considerable and depends mainly on (1) the complexity of the simulated system (2) the simulated time scale (3) the simulation method (4) the efficiency of used hardware and software algorithms. Carried out MD simulations nowadays may still take weeks of calculation on high end computers. In practice, biologically relevant processes, as e.g. protein folding, take usually place above the time scale of milli seconds. They can take up to the order of some thousands of seconds (in case of the folding of membrane proteins). Molecular dynamics computer simulations have reached the scale of micro seconds for simulations of systems where each atom was described and simulated over time.(Lindahl, 2008) Nevertheless, MD has risen to an important promoter methodology for many different fields of application. By replacing bunches of atoms by artificial particles, complexity of the systems can be reduced. This method is called the coarse grain method (CG). Biggin and Bond (2008) found an acceleration of their simulation processes for self assembling membrane / protein systems in water by factor 100. They estimated one to two days of calculation for a simulated time scale of 0.1 to 0.2 micro seconds for their systems. Implicit force fields like "IMPALA", aim to describe water and/or membrane molecules in simulations by a couple of simple and partially precalculable equations. “IMPALA” is a force field initially developed by our laboratory. Using this method, thousands of water and lipid molecules can be replaced, leading to a reduced complexity of the system to be simulated. "IMPALA"(Ducarme et al., 1998) based on the assumption of rigid peptides and aimed to find the insertion characteristics of such in membranes. Elimination of the necessity for simulating the aqueous and lipid phase atom by atom in the software package "Gromacs"(Berendsen et al., 1995) will permit both: a gain of speed, as it was already the case for the introduction of the coarse grain method, and a gain of precision by turning rigid molecules flexible through "Gromacs". Our current work is the integration of the "IMPALA" implicit force field into "Gromacs". Biggin, P.C. & Bond, P.J. Molecular dynamics simulations of membrane proteins. Methods Mol. Biol. 443, 147-60(2008). Berendsen, et al. (1995) Comp. Phys. Comm. 91: 43-56. Ducarme, P., Rahman, M. & Brasseur, R. IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies. Proteins 30, 357-71(1998). Lindahl, E.R. (2008). Molecular dynamics simulations. Methods Mol. Biol. 443, 3-23. [less ▲]

Multi-Scale Simulation of the Simian Immunodeficiency Virus Fusion Peptide.

in Journal of Physical Chemistry B (2012)

Fusion peptides of type I fusion glycoproteins are structural elements of several enveloped viruses which enable the fusion between host and virus membranes. It is generally suggested that these peptides ... [more ▼]

Fusion peptides of type I fusion glycoproteins are structural elements of several enveloped viruses which enable the fusion between host and virus membranes. It is generally suggested that these peptides can promote the early fusion steps by inducing membrane curvature and that they adopt a tilted helical conformation in membranes. Although this property has been the subject of several experimental and in silico studies, an extensive sampling of the membrane peptide interaction has not yet been done. In this study, we performed coarse-grained molecular dynamic simulations in which the lipid bilayer self-assembles around the peptide. The simulations indicate that the SIV fusion peptide can adopt two different orientations in a DPPC bilayer, a major population which adopts a tilted interfacial orientation and a minor population which is perpendicular to the bilayer. The simulations also indicate that for the SIV mutant that does not induce fusion in vitro the tilt is abolished. [less ▲]

Peplook, an efficient tool to predict conformation: application to cyclic peptides containing or not non natural residues

Conference (2011, February)

Impacts of the carbonyl group location of ester bond on interfacial properties of sugar-based surfactants: experimental and computational evidences

in Journal of Physical Chemistry B (2009), 113

Interfacial properties of surfactants are dependent on the conformation adopted by the hydrophilic headgroup or/and the hydrophobic tail at the boundary limit of two immiscible phases. Here, we ... [more ▼]

Interfacial properties of surfactants are dependent on the conformation adopted by the hydrophilic headgroup or/and the hydrophobic tail at the boundary limit of two immiscible phases. Here, we demonstrate the impacts of the carbonyl group (-CO-) location of the ester bond of sugar-based surfactants by comparing some properties of two closely related esters, octyl glucuronate and glucose octanoate, at the air-water interface. The carbonyl group location influences the rate and extent of interfacial adsorption and the rheology properties of sugar esters at the air-water interface, which were evaluated by dynamic surface tension and complex surface viscoelastic measurements. Octyl glucuronate adsorbs the fastest at the air-water interface whereas glucose octanoate reduces the dynamic surface tension at the lowest value and exhibits the highest film viscoelasticity. Differences are attributed to molecular conformation constraints inducing relevant changes to the surface coverage kinetic capacity and the interaction strengths of the octyl sugar ester adsorbed films at the air-water interface. All of the results are supported by the minimum cross-sectional area values per molecule determined by both experimental and computational approaches. [less ▲]

The N-terminal 12 residue long peptide of HIV gp41 is the minimal peptide sufficient to induce significant T-cell-like membrane destabilization in vitro.

in Journal of molecular biology (2006), 359(3), 597-609

Here, we predicted the minimal N-terminal fragment of gp41 required to induce significant membrane destabilization using IMPALA. This algorithm is dedicated to predict peptide interaction with a membrane ... [more ▼]

Here, we predicted the minimal N-terminal fragment of gp41 required to induce significant membrane destabilization using IMPALA. This algorithm is dedicated to predict peptide interaction with a membrane. We based our prediction of the minimal fusion peptide on the tilted peptide theory. This theory proposes that some protein fragments having a peculiar distribution of hydrophobicity adopt a tilted orientation at a hydrophobic/hydrophilic interface. As a result of this orientation, tilted peptides should disrupt the interface. We analysed in silico the membrane-interacting properties of gp41 N-terminal peptides of different length derived from the isolate BRU and from an alignment of 710 HIV strains available on the Los Alamos National Laboratory. Molecular modelling results indicated that the 12 residue long peptide should be the minimal fusion peptide. We then assayed lipid-mixing and leakage of T-cell-like liposomes with N-terminal peptides of different length as first challenge of our predictions. Experimental results confirmed that the 12 residue long peptide is necessary and sufficient to induce membrane destabilization to the same extent as the 23 residue long fusion peptide. In silico analysis of some fusion-incompetent mutants presented in the literature further revealed that they cannot insert into a modelled membrane correctly tilted. According to this work, the tilted peptide model appears to explain at least partly the membrane destabilization properties of HIV fusion peptide. [less ▲]