Combined results of theoretical molecular dynamic simulations and in vitro spectroscopic (circular dichroism and fluorescence) studies are presented, providing the atomistic and secondary structure details of the process by which a selected small molecule may destabilize the β-sheet ordered "amyloid" oligomers formed by the model undecapeptide of amyloid β-peptide 25-35 [Aβ(25-35)]. Aβ(25-35) was chosen because it is the shortest fragment capable of forming large β-sheet fibrils and retaining the toxicity of the full length Aβ(1-40/42) peptides. The conformational transition, that leads to the formation of β-sheet fibrils from soluble unordered structures, was found to depend on the environmental conditions, whereas the presence of myricetin destabilizes the self-assembly and antagonizes this conformational shift. In parallel, we analyzed several molecular dynamics trajectories describing the evolution of five monomer fragments, without inhibitor as well as in the presence of myricetin. Other well-known inhibitors (curcumin and (-)-tetracycline), found to be stronger and weaker Aβ(1-42) aggregation inhibitors, respectively, were also studied. The combined in vitro and theoretical studies of the Aβ(25-35) self-assembly and its inhibition contribute to understanding the mechanism of action of well-known inhibitors and the peptide amino acid residues involved in the interaction leading to a rational drug design of more potent new molecules able to antagonize the self-assembly process.

In this study, nascent silk nanoribbons (SNRs) with an average thickness of 0.4 nm were extracted from natural silkworm silk by partially dissolving degummed silk (DS) in sodium hydroxide (NaOH)/urea solution at −12 °C. In this gentle treatment, the solvent could not destroy the nanofibrillar structure completely, but the chosen conditions would influence the dimensions of resulting SNRs. Molecular dynamics simulations of silk models indicated that the potential of mean force required to break hydrogen bonds between silk fibroin chains was 40% larger than that of van der Waals interactions between β-sheet layers, allowing the exfoliating treatment. It was found that the resulting SNRs contained a single β-sheet layer and amorphous silk fibroin molecules, which could be considered as the basic building block of DS consisting of hierarchical structures. The demonstrated technique for extracting ultrathin SNRs having the height of a single β-sheet layer may provide a useful pathway for creating stronger and tougher silk-based materials and/or adding functionality and durability in materials for various applications. The hierarchical structure model based on SNRs may afford more insight into the structure and property relationship of fabricating silk-based materials.

Molecular dynamics simulations have been used to investigate the conformational transition behavior in amorphous polyethylene with different chain lengths across the glass transition temperature (T(g)). In the present study, we examined the barrier height of conformational transition rates in different states. It was found that two lines of the logarithmic rates versus inverse temperature in the melt state and in the glass state are evidently different. The two lines have an intersection, which indicates T(g) well. The barrier height in the glass state was unexpectedly observed lower than that in the melt state. For gaining better understanding of the transition barrier reduction, we analyzed motion heterogeneity of the systems and found the torsional transition rate distribution becoming gradually heterogeneous when the temperature went down to the glass state. The result indicates that the motion heterogeneity was caused by the torsion transition being "frozen". The frozen torsions made the system into a nonequilibrium state and possess a novel transition behavior, which accounted for most of the transitions that started at a location close to top of barrier, and also the enhancement of a small magnitude of transition jumps.

Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein–coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700 ns molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P1) based on recently released crystal structure of that receptor with an antagonist. We found that the initial movements of amino acid residues occurred in the area of highly conserved W2696.48 in TM6 which is close to the ligand binding location. Those residues located in the central part of the receptor and adjacent to kinks of TM helices comprise of a transmission switch. Side chains movements of those residues were coupled to the movements of water molecules inside the receptor which helped in the gradual opening of intracellular part of the receptor. The most stable parts of the protein were helices TM1 and TM2, while the largest movement was observed for TM7, possibly due to the short intracellular part starting with a helix kink at P7.50, which might be the first helix to move at the intracellular side. We show for the first time the detailed view of the concerted action of the transmission switch and Trp (W6.48) rotamer toggle switch leading to redirection of water molecules flow in the central part of the receptor. That event is a prerequisite for subsequent changes in intracellular part of the receptor involving water influx and opening of the receptor structure.

Large-scale coarse-grained molecular dynamics simulations have been performed to investigate the self-assemblies of dodecyltrimethylammonium bromide (DTAB) and gemini surfactants 12-S-12 (S = 6, 14, and 20). At the concentrations investigated, the surfactants experience fast aggregation of monomers into oligomers until the cluster numbers reach maxima. For DTAB, larger aggregates grow at the expense of monomers, but for gemini surfactants, the growth of clusters is accomplished via the merging of oligomers. In the final stage, spherical and worm-like micelles coexist in the systems of DTAB and 12-6-12, and in gemini systems with longer spacers, namely, 12-14-12 and 12-20-12, well-defined vesicles are formed through expansion and curving of bilayer-like structures. Through detailed analysis of the vesicle structures, many of the 12-20-12 surfactants are found to have their headgroups at different surfaces, with the spacers bridging the inner and outer surface of the vesicle.

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Molecular dynamics simulation has been performed on water/surfactant film rupture in order to investigate foam stability. A periodic boundary film model which was simulated in a lateral dimension of 8 x 8 nm(2) for 4 ns was established to stand for a part of a foam bubble. On the basis of critical film thickness, which is the lowest thickness before film rupture, a stability index was calculated to describe the capabilities of surfactants to stabilize water films. We investigated the influence of film size and simulation duration on the critical thickness and proved that our model is reasonable. The stability index versus surfactant concentration curve suggests that the capabilities of three surfactants-linear alkylbenzene sulfonate (LAS), sodium dodecyl sulfate (SDS), and heptaethylene glycol monododecyl ether (C(12)E(7))-in stabilization of water film decrease in the order of SDS > LAS > C(12)E(7). In the present study, the simulated results have been validated by the foam generation and decay experiment results, thus indicating that this method of predicting the stability of water/surfactant film is feasible.

Molecular dynamics simulation has been adopted in investigation of different glass transition behaviors of the bulk and the freestanding thin films (about 8 nm) of atactic polypropylene (a-PP). For characterization of glass transition temperature (T(g)) of above systems, both the specific volume and the local conformational transition rate of the systems were examined. The T(g) characterization from the local conformational transition rate of polymer chains was recently developed. Our simulation results show that the films have lower T(g) than the bulk, and the descent of T(g) is in a range of 30 approximately 10 K. These are consistent with experiments. a-PP chain consists of meso-dyad and racemic-dyad, the above results are obtained from both dyads. Individual contribution of the stereoregular dyads to the conformational transition rate was further studied. It was revealed that T(g) obtained singly from the meso-dyads was almost the same with T(g) individually from the racemic-dyads, although the racemic-dyads have much lower transition rate and higher transition barrier than the meso-dyads. In the present study, the reason for the thin films having lower T(g) than the bulk is attributed to the novel behavior that the films have lower transition rate and higher barrier than the bulk when it is below T(g). Such behavior was discussed according to the "coupling rotation" of the dihedrals, which depends on the increase of free volume and the inhibition of kinetic energy.