Data of the molecular dynamics simulations of mutations in the human connexin46 docking interface

The structure of hCx26 derived from the X-ray analysis was used to generate a homology model for hCx46. Interacting connexin molecules were used as starting model for the molecular dynamics (MD) simulation using NAMD and allowed us to predict the dynamic behavior of hCx46wt and the cataract related mutant hCx46N188T as well as two artificial mutants hCx46N188Q and hCx46N188D. Within the 50 ns simulation time the docked complex composed of the mutants dissociate while hCx46wt remains stable. The data indicates that one hCx46 molecule forms 5-7 hydrogen bonds (HBs) with the counterpart connexin of the opposing connexon. These HBs appear essential for a stable docking of the connexons as shown by the simulation of an entire gap junction channel and were lost for all the tested mutants. The data described here are related to the research article entitled "The cataract related mutation N188T in human connexin46 (hCx46) revealed a critical role for residue N188 in the docking process of gap junction channels" (Schadzek et al., 2015) [1].

Understanding and modulating the competitive surface-adsorption of proteins through coarse-grained molecular dynamics simulations

It is now well accepted that cellular responses to materials in a biological medium reflect greatly the adsorbed biomolecular layer, rather than the material itself. Here, we study by molecular dynamics simulations the competitive protein adsorption on a surface (Vroman effect), i.e. the non-monotonic behavior of the amount of protein adsorbed on a surface in contact with plasma as functions of contact time and plasma concentration. We find a complex behavior, with regimes during which small and large proteins are not necessarily competing between them, but are both competing with others in solution ("cooperative" adsorption). We show how the Vroman effect can be understood, controlled and inverted.

Understanding and modulating the competitive surface-adsorption of proteins through coarse-grained molecular dynamics simulations

It is now well accepted that cellular responses to materials in a biological medium reflect greatly the adsorbed biomolecular layer, rather than the material itself. Here, we study by molecular dynamics simulations the competitive protein adsorption on a surface (Vroman effect), i.e. the non-monotonic behavior of the amount of protein adsorbed on a surface in contact with plasma as functions of contact time and plasma concentration. We find a complex behavior, with regimes during which small and large proteins are not necessarily competing between them, but are both competing with others in solution ("cooperative" adsorption). We show how the Vroman effect can be understood, controlled and inverted.

Molecular dynamics simulations of threadlike cetyltrimethylammonium chloride micelles: effects of sodium chloride and sodium salicylate salts

We use atomistic molecular dynamics simulations to probe the effects of added sodium chloride (NaCl) and sodium salicylate (NaSal) salts on the spherical-to-threadlike micelle shape transition in aqueous solutions of cetyltrimethylammonium chloride (CTAC) surfactants. Long threadlike micelles are found to be unstable and break into spherical micelles at low concentrations or NaCl, but remain stable for 20 ns above a threshold value of [NaCl] approximate to 3.0 M, which is about 2.5 times larger than the experimental salt concentration at which the transition between spherical and rodlike micelles occurs. The chloride counterions associate weakly oil the surface of the CTAC micelles with the degree of counterion dissociation decreasing slightly with increasing [NaCl] on spherical micelles, but dropping significantly on the threadlike micelles tit high [NaCl]. This effect indicates that the electrolyte ions drive the micellar shape transition by screening the electrostatic repulsions between the micellar headgroups, The aromatic salicylate counterions, on the other hand, penetrate inside the micelle with their hydrophilic groups staying in the surfactant headgroup region and the hydrophobic groups partially embedded into the hydrophobic core of the micelle. The strong association of the salicylate ions with the surfactant headgroups leads to dense packing of the surfactant molecules, which effectively reduces the surface area per surfactant, and increases intramicellar ordering of the surfactant headgroups, favoring the formation of long threadlike micelles. Simulation predictions of the geometric and electrostatic properties of the spherical and threadlike micelles are in good agreement with experiments.

Ligand dissociation from estrogen receptor is mediated by receptor dimerization: Evidence from molecular dynamics simulations

Estrogen Receptor (ER) is an important target for pharmaceutical design. Like other ligand-dependent transcription factors, hormone binding regulates ER transcriptional activity. Nevertheless, the mechanisms by which ligands enter and leave ERs and other nuclear receptors remain poorly understood. Here, we report results of locally enhanced sampling molecular dynamics simulations to identify dissociation pathways of two ER ligands [the natural hormone 17 beta-estradiol (E-2) and the selective ER modulator raloxifene (RAL)] from the human ER alpha ligand-binding domain in monomeric and dimeric forms. E-2 dissociation occurs via three different pathways in ER monomers. One resembles the mousetrap mechanism (Path I), involving repositioning of helix 12 (H12), others involve the separation of H8 and H11 (Path II), and a variant of this pathway at the bottom of the ligand-binding domain (Path II`). RAL leaves the receptor through Path I and a Path I variant in which the ligand leaves the receptor through the loop region between H11 and H12 (Path I`). Remarkably, ER dimerization strongly suppresses Paths II and II` for E-2 dissociation and modifies RAL escape routes. We propose that differences in ligand release pathways detected in the simulations for ER monomers and dimers provide an explanation for previously observed effects of ER quaternary state on ligand dissociation rates and suggest that dimerization may play an important, and hitherto unexpected, role in regulation of ligand dissociation rates throughout the nuclear receptor family.

PACKMOL: A Package for Building Initial Configurations for Molecular Dynamics Simulations

Adequate initial configurations for molecular dynamics simulations consist of arrangements of molecules distributed in space in such a way to approximately represent the system`s overall structure. In order that the simulations are not disrupted by large van der Waals repulsive interactions, atoms from different molecules Must keep safe pairwise distances. Obtaining Such a molecular arrangement can be considered it packing problem: Each type molecule must satisfy spatial constraints related to the geometry of the system, and the distance between atoms of different molecules Must be greater than some specified tolerance. We have developed a code able to pack millions of atoms. grouped in arbitrarily complex molecules, inside a variety of three-dimensional regions. The regions may be intersections of spheres, ellipses, cylinders, planes, or boxes. The user must provide only the structure of one molecule of each type and the geometrical constraints that each type of molecule must satisfy. Building complex mixtures, interfaces, solvating biomolecules in water, other solvents, or mixtures of solvents, is straight forward. In addition. different atoms belonging to the same molecule may also be restricted to different spatial regions, in Such a way that more ordered molecular arrangements call be built, as micelles. lipid double-layers, etc. The packing time for state-of-the-art molecular dynamics systems varies front a few seconds to a few Minutes in a personal Computer. The input files are simple and Currently compatible with PDB, Tinker, Molden, or Moldy coordinate files. The package is distributed as free software and call be downloaded front http://www.ime.unicamp.br/similar to martinez/packmol/. (C) 2009 Wiley Periodicals. Inc. J Comput Chem 30: 2157-2164, 2009

Distribution of neutral prilocaine in a phospholipid bilayer: Insights from molecular dynamics simulations

In this work, we report a 20-ns constant pressure molecular dynamics simulation of prilocaine (PLC), in amine-amide local anesthetic, in a hydrated liquid crystal bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine. The partition of PLC induces the lateral expansion of the bilayer and a concomitant contraction in its thickness. PLC molecules are preferentially found in the hydrophobic acyl chains region, with a maximum probability at similar to 12 angstrom from the center of the bilayer (between the C(4) and C(5) methylene groups). A decrease in the acyl chain segmental order parameter, vertical bar S-CD vertical bar, compared to neat bilayers, is found, in good agreement with experimental H-2-NMR studies. The decrease in vertical bar S-CD vertical bar induced by PLC is attributed to a larger accessible volume per lipid in the acyl chain region. (C) 2008 Wiley Periodicals, Inc.

Molecular Dynamics simulations of track formation at different ensembles

A series of Molecular Dynamics simulations of thermal spikes has been run in zircon. For two different ensembles: microcanonical one and a combination of microcanonical one acting on the simulation core with Langevin one on the side walls of simulation. Depending on the used ensemble, different track-formation threshold energies were found. When the combined ensemble is carried out, the total energy of the simulations varies with the temperature which can influence how annealing fission-track models should deal with the lattice recovery. A fission-track annealing model is tested with the simulation results. © 2012 Elsevier Ltd. All rights reserved.

On the unzipping mechanisms of carbon nanotubes: Insights from reactive molecular dynamics simulations

Unzipping carbon nanotubes (CNTs) is considered one of the most promising approaches for the controlled and large-scale production of graphene nanoribbons (GNR). These structures are considered of great importance for the development of nanoelectronics because of its dimensions and intrinsic nonzero band gap value. Despite many years of investigations some details on the dynamics of the CNT fracture/unzipping processes remain unclear. In this work we have investigated some of these process through molecular dynamics simulations using reactive force fields (ReaxFF), as implemented in the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) code. We considered multi-walled CNTs of different dimensions and chiralities and under induced mechanical stretching. Our preliminary results show that the unzipping mechanisms are highly dependent on CNT chirality. Well-defined and distinct fracture patterns were observed for the different chiralities. Armchair CNTs favor the creation of GNRs with well-defined armchair edges, while zigzag and chiral ones produce GNRs with less defined and defective edges. © 2012 Materials Research Society.

Elucidating the real-time Ag nanoparticle growth on alpha-Ag2WO4 during electron beam irradiation: experimental evidence and theoretical insights

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular dynamics simulations of sheared brush-like systems

Mit Hilfe von Molekulardynamik-Simulationen untersuchen wir bürstenartige Systeme unter guten Lösungsmittelbedingungen. Diese Systeme sind, dank ihren vielfältigen Beschaffenheiten, die von Molekularparametern und äußeren Bedingungen abhängig sind, wichtig für viele industrielle Anwendungen. Man vermutet, dass die Polymerbürsten eine entscheidende Rolle in der Natur wegen ihrer einzigartigen Gleiteigenschaften spielen. Ein vergröbertes Modell wird verwendet, um die strukturellen und dynamischen Eigenschaften zweier hochkomprimierter Polymerbürsten, die eine niedrige Reibung aufweisen, zu untersuchen. Allerdings sind die Lubrikationseigenschaften dieser Systeme, die in vielen biologischen Systemen vorhanden sind, beeinflußt. Wir untersuchen so-genannte "weiche Kolloide", die zwischen den beiden Polymerbürsten eingebettet sind, und wie diese Makroobjekte auf die Polymerbürsten wirken.rnrnNicht-Gleichgewichts-Molekulardynamik-Simulationen werden durchgeführt, in denen die hydrodynamischen Wechselwirkungen durch die Anwendung des DPD-Thermostaten mit expliziten Lösungsmittelmolekülen berücksichtigt werden. Wir zeigen, dass die Kenntnis der Gleichgewichtseigenschaften des Systems erlaubt, dynamische Nichtgleichgewichtsigenschaften der Doppelschicht vorherzusagen.rnrnWir untersuchen, wie die effektive Wechselwirkung zwischen kolloidalen Einschlüßen durch die Anwesenheit der Bürsten (in Abhängigkeit der Weichheit der Kolloide und der Pfropfdichte der Bürsten) beeinflußt wird. Als nächsten Schritt untersuchen wir die rheologische Antwort von solchen komplexen Doppelschichten auf Scherung. Wir entwickeln eine Skalen-Theorie, die die Abhängigkeit der makroskopischen Transporteigenschaften und der lateralen Ausdehnung der verankerten Ketten von der Weissenberg Zahl oberhalb des Bereichs, in dem die lineare Antwort-Theorie gilt, voraussagt. Die Vorhersagen der Theorie stimmen gut mit unseren und früheren numerischen Ergebnissen und neuen Experimenten überein. Unsere Theorie bietet die Möglichkeit, die Relaxationszeit der Doppelschicht zu berechnen. Wenn diese Zeit mit einer charakteristischen Längenskala kombiniert wird, kann auch das ''transiente'' (nicht-stationäre) Verhalten beschrieben werden.rnrnrnWir untersuchen die Antwort des Drucktensors und die Deformation der Bürsten während der Scherinvertierung für grosse Weissenberg Zahlen. Wir entwickeln eine Vorhersage für die charakteristische Zeit, nach der das System wieder den stationären Zustand erreicht.rnrnrnElektrostatik spielt eine bedeutende Rolle in vielen biologischen Prozessen. Die Lubrikationseigenschaften der Polymerbürsten werden durch die Anwesenheit langreichweitiger Wechselwirkungen stark beeinflusst. Für unterschiedliche Stärken der elektrostatischen Wechselwirkungen untersuchen wir rheologische Eigenschaften der Doppelschicht und vergleichen mit neutralen Systemen. Wir studieren den kontinuierlichen Übergang der Systemeigenschaften von neutralen zu stark geladenen Bürsten durch Variation der Bjerrumlänge und der Ladungsdichte.

Molecular Dynamics Simulations of the d(TAT) Triple Helix

Molecular dynamics (MD) simulations have been used to study the dynamical and time-averaged characteristics of the DNA triple helix d(T)10âd(A)10âd(T)10. The structures sampled during the trajectory resemble closely the B-type model for the DNA triplex proposed on the basis of NMR data, although there are some subtle differences. Alternative P- and A-type conformations for the triplex, suggested from X-ray experiments, are not predicted to contribute significantly to the structure of the DNA triplex in solution. Comparison with the best available experimental data supports the correctnes of the MD-generated structures. The analysis of the collected data gives a detailed picture of the characteristics of triple-helix DNA. A new and interesting pattern of hydration, specific for triplex DNA, is an important observation. The results suggest that molecular dynamics can be useful for the study of novel nucleic acid structures.