Bending Free Energy from Simulation: Correspondence of Planar and Inverse Hexagonal Lipid Phases

Sodt, Alexander J.; Pastor, Richard W.

doi:10.1016/j.bpj.2013.03.048

Cited by 71 publications

(100 citation statements)

References 54 publications

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“…1, respectively). The fluctuations in

{\overset{F}{true}}^{'} (0)

appear to increase after 100 ns, but the larger fluctuations are similar to those calculated by Sodt and Pastor (Sodt and Pastor 2013; Sodt and Pastor 2014). The fluctuations in K A are more constant over the trajectory.…”

Section: Methodssupporting

confidence: 86%

“…Recent simulations have shown excellent agreement with experiment for the spontaneous curvature of DOPE in both the H II and lamellar phase (Sodt and Pastor 2013), and positive curvature generation by the amphipathic helix from ArfGAP1 was readily quantifiable (Sodt and Pastor 2014). The present study considers curvature generation and related bilayer perturbations (thinning and chain disruption) by the surface bound AMPs piscidin 1 (p1) and piscidin 3 (p3) in 4 different bilayers: 3:1 DMPC/DMPG, 3:1 POPC/POPG, 1:1 POPE/POPG, and 4:1 POPC/chol.…”

Section: Introductionmentioning

confidence: 80%

“…(1) (Chen and Rand 1998; Fuller and Rand 2001; Gruner et al 1986; Rand et al 1990). These quantities can also be obtained by direct simulation of the H II phase, where the pressure difference in the middle of the water pore and the acyl chain region is equated to the osmotic pressure difference that is measured experimentally (Sodt and Pastor 2013). …”

Section: Theorymentioning

confidence: 99%

See 2 more Smart Citations

The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length

et al. 2014

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The initial steps of membrane disruption by antimicrobial peptides (AMPs) involve binding to bacterial membranes in a surface-bound (S) orientation. To evaluate the effects of lipid composition on the S state, molecular dynamics simulations of the AMPs piscidin 1 (p1) and piscidin 3 (p3) were carried out in 4 different bilayers: 3:1 DMPC/DMPG, 3:1 POPC/POPG, 1:1 POPE/POPG, and 4:1 POPC/cholesterol. In all cases, the addition of 1:40 piscidin caused thinning of the bilayer, though thinning was least for DMPC/DMPG. The peptides also insert most deeply into DMPC/DMPG, spanning the region from the bilayer midplane to the head groups, and thereby only mildly disrupting the acyl chains. In contrast, the peptides insert less deeply in the palmitoyl-oleoyl containing membranes, do not reach the midplane, and substantially disrupt the chains; i.e., the neighboring acyl chains bend under the peptide, forming a basket-like conformation. Curvature free energy derivatives calculated from the simulation pressure profiles reveal that the peptides generate positive curvature in membranes with palmitoyl and oleoyl chains but negative curvature in those with myristoyl chains. Curvature inductions predicted with a continuum elastic model follow the same trends, though the effect is weaker and a small negative curvature induction is obtained in POPC/POPG. These results do not directly speak to the relative stability of the inserted (I) states or ease of pore formation, which requires the free energy pathway between the S and I states. Nevertheless, they do highlight the importance of lipid composition and acyl chain packing.

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“…1, respectively). The fluctuations in

{\overset{F}{true}}^{'} (0)

Section: Methodssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 80%

Section: Theorymentioning

confidence: 99%

See 1 more Smart Citation

The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length

et al. 2014

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“…However, a recent study shows that CHARMM36 lipid parameters perform well in the case of high-curvature inverse hexagonal phases. 66 Additionally, Piggot et al 4 report CHARMM36 to be the only one of the force fields they examined to reproduce correctly also the C2 carbon atom deuterium order parameters for both DPPC and POPC (palmitoyloleoylphosphatidylcholine) lipids. This means the C2 carbon atom which is facing the head group could be assumed to sample the same conformations as the lipids in the NMR experiments.…”

Section: Resultsmentioning

confidence: 99%

Phosphatidylcholine reverse micelles on the wrong track in molecular dynamics simulations of phospholipids in an organic solvent

Vierros

Sammalkorpi

2015

The Journal of Chemical Physics

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Here, we examine a well-characterized model system of phospholipids in cyclohexane via molecular dynamics simulations using a force field known for reproducing both phospholipid behavior in water and cyclohexane bulk properties to a high accuracy, CHARMM36, with the aim of evaluating the transferability of a force field parametrization from an aqueous environment to an organic solvent. We compare the resulting reverse micelles with their expected experimental shape and size, and find the model struggles with reproducing basic, experimentally known reverse micellar structural characteristics for common phosphadidylcholine lipids such as 1,2-dipalmitoyl-snglycero-3-phosphatidylcholine (DPPC), 1,2-dioleyl-sn-glycero-3-phosphatidylcholine (DOPC), and 1,2-dilinoleyl-sn-glycero-3-phosphatidylcholine (DLPC) in cyclohexane solvent. We find evidence that the deviation from the experimental behavior originates from an underestimation of the lipid tail-cyclohexane interaction in the model. We compensate for this, obtain reverse micellar structures within the experimentally expected range, and characterize these structurally in molecular detail. Our findings indicate extra caution and verification of model applicability is warranted in simulational studies employing standard biomolecular models outside the usual aqueous environment. C 2015 AIP Publishing LLC. [http://dx

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“…First, the absence of this effect in H II monolayers [53] suggests that any κ eff increase should arise from positive curvature. Second, the CT simulations in [6], using a soft, highly coarse-grained lipid model showed no evidence of anharmonicity, suggesting that the effect might originate from stronger repulsions in the more physical model used here.…”

mentioning

confidence: 99%

Exploiting Lipid Permutation Symmetry to Compute Membrane Remodeling Free Energies

2016

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A complete physical description of membrane remodeling processes, such as fusion or fission, requires knowledge of the underlying free energy landscapes, particularly in barrier regions involving collective shape changes, topological transitions, and high curvature, where Canham-Helfrich (CH) continuum descriptions may fail. To calculate these free energies using atomistic simulations, one must address not only the sampling problem due to high free energy barriers, but also an orthogonal sampling problem of combinatorial complexity stemming from the permutation symmetry of identical lipids. Here, we solve the combinatorial problem with a permutation reduction scheme to map a structural ensemble into a compact, nondegenerate subregion of configuration space, thereby permitting straightforward free energy calculations via umbrella sampling. We applied this approach, using a coarse-grained lipid model, to test the CH description of bending and found sharp increases in the bending modulus for curvature radii below 10 nm. These deviations suggest that an anharmonic bending term may be required for CH models to give quantitative energetics of highly curved states. DOI: 10.1103/PhysRevLett.117.188102 Membrane remodeling is essential for many cellular transport functions, notably fusion [1] and fission [2]. However, despite continued interest, the underlying lipidic mechanisms and energetics are not fully understood. Atomistic and near-atomistic molecular dynamics (MD) simulations provide sufficient temporal and spatial resolution to probe lipidic mechanisms. However, standard MD fails to reach the high energy barriers (≫k B T) which often dictate mechanisms and kinetics. Biasing methods are thus required to address the sampling problem for high energy barriers.An additional and ubiquitous obstacle, in both describing and biasing lipidic transitions, is the N! degeneracy of lipid configuration space arising from the permutation symmetry of N identical lipids. The same combinatorial symmetry lies at the heart of the Gibbs paradox [3][4][5], which is resolved by a 1=N! scaling of the partition function, to account for physically indistinguishable (degenerate) states.In contrast to this straightforward analytical correction, this permutation symmetry poses a severe challenge to atomistic simulations and free energy calculations involving lipids: sampling the space of degenerate states (via self-diffusion) shrouds the collective structural changes of interest and precludes the use of lipidic collective coordinate biasing schemes. Accordingly, special purpose methods (that circumvent this hindrance) have been developed to direct lipidic transitions using boundary conditions [6,7], external guiding potentials [8,9], probe particles [10], density biasing [11,12], and single-lipid restraints [13,14].Here, we describe and apply a rigorous method to directly address this N! degeneracy, using permutation reduction (PR) [15,16]. The method exploits permutation symmetry by remapping structures from the full N! degenerate configur...

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Bending Free Energy from Simulation: Correspondence of Planar and Inverse Hexagonal Lipid Phases

Cited by 71 publications

References 54 publications

The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length

The Curvature Induction of Surface-Bound Antimicrobial Peptides Piscidin 1 and Piscidin 3 Varies with Lipid Chain Length

Phosphatidylcholine reverse micelles on the wrong track in molecular dynamics simulations of phospholipids in an organic solvent

Exploiting Lipid Permutation Symmetry to Compute Membrane Remodeling Free Energies

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