NanoPores

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Last Updated: Monday, 19 August 2013 14:42

"Spontaneous Imbibition in Nanopores of Different Roughness and Wettability" by M.R. Stukan, P. Ligneul, J.P. Crawshaw and E.S. Boek. Langmuir, 2010, DOI:10.1021/la101995t

The spontaneous imbibition of liquid in nanopores of different roughness is investigated using coarse grain molecular dynamics (MD) simulation. The numerical model is presented and the simplifying assumptions are discussed in detail. The molecular-kinetic theory introduced by Blake is used to describe the effect of dynamic contact angle on fluid imbibition. The capillary roughness is modeled using a random distribution of coarse grained particles forming the wall. The Lucas−Washburn equation is used as a reference for analyzing the imbibition curves obtained by simulation. Due to the statistical nature of MD processing, a comprehensive approach was made to average and smooth the data to accurately define a contact angle. The results are discussed in terms of effective hydrodynamic and static capillary radii and their difference as a function of roughness and wettability.

Collagen

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Last Updated: Monday, 19 August 2013 14:42

"Coarse-Grained Model of Collagen Molecules Using an Extended MARTINI Force Field" by A. Gautieri, A. Russo, S. Vesentini, A. Redaelli, M.J. Buehler. J. Chem. Theory Comput., 2010, 6, 1210–1218

Collagen is the most abundant protein in the human body, providing mechanical stability, elasticity, and strength to connective tissues such as tendons, ligaments, and bone. Here, we report an extension of the MARTINI coarse-grained force field, originally developed for lipids, proteins, and carbohydrates, used to describe the structural and mechanical properties of collagen molecules. We identify MARTINI force field parameters to describe hydroxyproline amino acid residues and for the triple helical conformational structure found in collagen. We validate the extended MARTINI model through direct molecular dynamics simulations of Young’s modulus of a short 8-nm-long collagen-like molecule, resulting in a value of approximately 4 GPa, in good agreement with earlier full atomistic simulations in explicit solvent as well as experimental results. We also apply the extended MARTINI model to simulate a 300-nm-long human type I collagen molecule with the actual amino acid sequence and calculate its persistence length from molecular dynamics trajectories. We obtain a value of 51.5 ± 6.7 nm for the persistence length, which is within the range of earlier experimental results. Our work extends the applicability of molecular models of collagenous tissues by providing a modeling tool to study collagen molecules and fibrils at much larger scales than accessible to existing full atomistic models, while incorporating key chemical and mechanical features and thereby presenting a powerful approach to computational materiomics.

Polarizable water

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Last Updated: Monday, 19 August 2013 14:42

 

"Polarizable Water Model for the Coarse-Grained MARTINI Force Field" by Semen O. Yesylevskyy, Lars V. Schäfer, Durba Sengupta, and Siewert J. Marrink, PLoS Comp. Biol. 6:e1000810, 2010. open access

Coarse-grained (CG) simulations have become an essential tool to study a large variety of biomolecular processes, exploring temporal and spatial scales inaccessible to traditional models of atomistic resolution. One of the major simplifications of CG models is the representation of the solvent, which is either implicit or modeled explicitly as a vanderWaals particle. The effect of polarization, and thus a proper screening of interactions depending on the local environment, is absent. Given the important role of water as a ubiquitous solvent in biological systems, its treatment is crucial to the properties derived from simulation studies. Here, we parameterize a polarizable coarse-grained water model to be used in combination with the CG MARTINI force field. Using a three-bead model to represent four water molecules, we show that the orientational polarizability of real water can be effectively accounted for. This has the consequence that the dielectric screening of bulk water is reproduced. At the same time, we parameterized our new water model such that bulk water density and oil/water partitioning data remain at the same level of accuracy as for the standard MARTINI force field. We apply the new model to two cases for which current CG force fields are inadequate. First, we address the transport of ions across a lipid membrane. The computed potential of mean force show that the ions now naturally feel the change in dielectric medium when moving from the high dielectric aqueous phase toward the low dielectric membrane interior. In the second application we consider the electroporation process of both an oil slab and a lipid bilayer. The electrostatic field drives the formation of water filled pores in both cases, following a similar mechanism as seen with atomistically detailed models.

 

 

Rhodopsin in cubic phase

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Last Updated: Wednesday, 21 August 2013 11:44

George Khelashvili , Pedro Blecua Carrillo Albornoz , Niklaus Johner , Sayan Mondal , Martin Caffrey , and Harel Weinstein. Why GPCRs behave differently in cubic and lamellar lipidic mesophases. J. Am. Chem. Soc., Just Accepted Manuscript, 2012. DOI: 10.1021/ja3056485

Recent successes in the crystallographic determination of structures of transmembrane proteins in the G protein-coupled receptor (GPCR) family have established the lipidic cubic phase (LCP) environment as the medium of choice for growing structure-grade crystals by the method termed “in meso”. The understanding of in meso crystallogenesis is currently at a descriptive level. To enable an eventual quantitative, energy-based description of the nucleation and crystallization mechanism, we have examined the properties of the lipidic cubic phase system and the dynamics of the GPCR rhodopsin reconstituted into the LCP with coarse-grained molecular dynamics simulations with the Martini force-field. Quantifying the differences in the hydrophobic/hydrophilic exposure of the GPCR to lipids in the cubic and lamellar phases we found that the highly curved geometry of the cubic phase provides more efficient shielding of the protein from unfavorable hydrophobic exposure, which leads to a lesser hydrophobic mismatch and less unfavorable hydrophobic-hydrophilic interactions between the protein and lipid-water interface in the LCP, compared to the lamellar phase. Since hydrophobic mismatch is considered a driving force for oligomerization, the differences in exposure mismatch energies between the LCP and the lamellar structures suggest that the latter provide a more favorable setting in which GPCRs can oligomerize as a prelude to nucleation and crystal growth. These new findings lay the foundation for future investigations of in meso crystallization mechanisms related to the transition from the LCP to the lamellar phase, and studies aimed at an improved rational approach for generating structure-quality crystals of membrane proteins.

 

Peptide amphiphile self-assembly

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Last Updated: Wednesday, 21 August 2013 11:44

One-Sun Lee, Vince Cho, and George C. Schatz. Modeling the Self-Assembly of Peptide Amphiphiles into Fibers Using Coarse-Grained Molecular Dynamics. Nano Lett., ASAP, 2012. DOI: 10.1021/nl302487m

We have studied the self-assembly of peptide amphiphiles (PAs) into a cylindrical micelle fiber starting from a homogeneous mixture of PAs in water using coarse-grained molecular dynamics simulations. Nine independent 16 μs runs all show spontaneous fiber formation in which the PA molecules first form spherical micelles, and then micelles form a three-dimensional network via van der Waals interactions. As the hydrophobic core belonging to the different micelles merge, the three-dimensional network disappears and a fiber having a diameter of 80 Å appears. In agreement with atomistic simulation results, water molecules are excluded from the hydrophobic core and penetrate to 15 Å away from the axis of fiber. About 66% of the surface of fiber is covered with the IKVAV epitope, and 92% of the epitope is exposed to water molecules.

 

ATP synthase

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Last Updated: Wednesday, 21 August 2013 11:21

Karen M. Davies, Claudio Anselmi, Ilka Wittig, José D. Faraldo-Gómez, and Werner Kühlbrandt. Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the mitochondrial cristae. PNAS, 2012, ASAP. doi:10.1073/pnas.1204593109

We used electron cryotomography of mitochondrial membranes from wild-type and mutant Saccharomyces cerevisiae to investigate the structure and organization of ATP synthase dimers in situ. Subtomogram averaging of the dimers to 3.7 nm resolution revealed a V-shaped structure of twofold symmetry, with an angle of 86° between monomers. The central and peripheral stalks are well resolved. The monomers interact within the membrane at the base of the peripheral stalks. In wild-type mitochondria ATP synthase dimers are found in rows along the highly curved cristae ridges, and appear to be crucial for membrane morphology. Strains deficient in the dimer-specific subunits e and g or the first transmembrane helix of subunit 4 lack both dimers and lamellar cristae. Instead, cristae are either absent or balloon-shaped, with ATP synthase monomers distributed randomly in the membrane. Computer simulations indicate that isolated dimers induce a plastic deformation in the lipid bilayer, which is partially relieved by their side-by-side association. We propose that the assembly of ATP synthase dimer rows is driven by the reduction in the membrane elastic energy, rather than by direct protein contacts, and that the dimer rows enable the formation of highly curved ridges in mitochondrial cristae.