Development of a ReaxFF Reactive Force Field for ternary phosphate-based bioactive glasses: input and analysis codes

Input and analysis codes to accompany the paper "Development of a ReaxFF Reactive Force Field for ternary phosphate-based bioactive glasses". Not all output files are included for space reasons, but the files given are sufficient to reproduce the methodology in the paper.Abstract of paper:Phosphate-based glasses (PBGs) in the CaO-Na2O-P2O5 system have diverse applications as biomaterials due to their unique dissolution properties. A reactive force field (ReaxFF) has been developed to simulate these materials at the atomic level. The ReaxFF parameters of PBGs, including the interaction between phosphorus and calcium atoms, have been developed using a published code based on genetic algorithms. The training data, including the atomic charges, atomic forces, bond and angle parameters and different differential energies are chosen and measured from static quantum-mechanical calculations and ab initio molecular dynamics of PBGs. We did different short- and medium-range structural analysis on the bulk simulated PBGs with different compositions to validate the developed potential. Radial and angular distribution functions and coordination numbers of network formers and modifiers as well as the network connectivity of the bioglass are in agreement with experimental and previous simulations using both shell-model classical force fields and ab initio simulated data; for example, the coordination number of phosphorus is 4.0. This successful development of ReaxFF parameters being able to describe the bulk PBGs enables us to work on dissolution behaviour of the glasses including the interaction of water molecules with PBGs in future works. </p

A reactive interatomic potential for the simulation of sodium phosphate glass

Input and analysis codes to accompany the paper "A reactive interatomic potential for the simulation of sodium phosphate glass", about to be submitted.  Not all output files are included for space reasons, but the files given are sufficient to reproduce the methodology in the paper.</p

Pulse electrodeposition of Co1−xZnx nanowire arrays: Magnetic improvement through electrolyte concentration, off-time between pulses and annealing

Using different electrolyte compositions and varying the off-time between pulses, Co1xZnx nanowire arrays were fabricated by ac pulse electrodeposition. The effect of deposition parameters on alloy contents was investigated by studying the microstructures and magnetic properties of as-deposited and annealed Co1xZnx nanowires. It is shown that Zn content in CoZn nanowires exponentially increases by increasing the zinc ions in the electrolyte. The Zn content initially increases to a maximum by increase in off-time between pulses and then falls off. Adding a certain amount of Zn to Co led to form amorphous CoZn nanowires. A significant increase in magnetization, coercivity and squareness of CoZn nanowires was observed after annealing. The rate of increase in magnetization of annealed samples was seen to be inversely proportional to their initial magnetization. Improvement of magnetic properties of annealed samples may be caused by magnetic cluster formation and pinning effect

Magnetic properties improvement through off time between pulses and annealing in pulse electrodeposited CoZn nanowires

CoZn alloy nanowire arrays embedded in anodic aluminum oxide (AAO) template were fabricated by alternative current (ac) pulse electrodeposition. Various off times between pulses in an electrolyte with constant concentration of Co+2 and Zn+2 and acidity of 4 were employed. The effect of deposition parameters on the alloy contents, microstructures and magnetic properties of CoxZn1−x nanowires were studied. It is shown that, Co content increased by increasing the off time between pulses. This phenomenon enables us to fabricate Zn and Co-rich nanowires by adjusting the off time during the deposition procedure. Increasing the off time more than 200 ms increased the coercivity and squareness of CoZn nanowire arrays. A significantincrease in the coercivity of CoZn nanowires was observed after annealing which was varied for the samples fabricated with different electrodeposition conditions. A coercivity of 1785 Oe was obtained for the annealed sample (a sample fabricated with 50 ms off time) from initially 240 Oe

Structural and functional effect of an oscillating electric field on the dopamine-D3 receptor: A molecular dynamics simulation study

Dopamine as a neurotransmitter plays a critical role in the functioning of the central nervous system. The structure of D3 receptor as a member of class A G-protein coupled receptors (GPCRs) has been reported. We used MD simulation to investigate the effect of an oscillating electric field, with frequencies in the range 0.6–800 GHz applied along the z-direction, on the dopamine-D3R complex. The simulations showed that at some frequencies, the application of an external oscillating electric field along the z-direction has a considerable effect on the dopamine-D3R. However, there is no enough evidence for prediction of changes in specific frequency, implying that there is no order in changes. Computing the correlation coefficient parameter showed that increasing the field frequency can weaken the interaction between dopamine and D3R and may decrease the Arg128{3.50}-Glu324{6.30} distance. Because of high stability of α helices along the z-direction, applying an oscillating electric field in this direction with an amplitude 10-time higher did not have a considerable effect. However, applying the oscillating field at the frequency of 0.6 GHz along other directions, such as X-Y and Y-Z planes, could change the energy between the dopamine and the D3R, and the number of internal hydrogen bonds of the protein. This can be due to the effect of the direction of the electric field vis-à-vis the ligands orientation and the interaction of the oscillating electric field with the dipole moment of the protein

Ligand-selective small molecule modulators of the constitutively active vGPCR US28

US28 is a broad-spectrum constitutively active G protein-coupled receptor encoded by the human cytomegalovirus (HCMV). It binds and scavenges multiple CC-chemokines as well as CX3CL1 (fractalkine) by constitutive receptor endocytosis to escape immune surveillance. We herein report the design and characterization of a novel library of US28-acting commercially available ligands based on the molecular descriptors of two previously reported US28-acting structures. Among these, we identify compounds capable of selectively recognizing CCL2-and CCL4-, but not CX3CL1-induced receptor conformations. Moreover, we find a direct correlation between the binding properties of small molecule ligands to CCLinduced conformations at the wild-type receptor and functional activity at the C-terminal truncated US28D300. As US28D300 is devoid of arrestin-recruitment and endocytosis, this highlights the potential usefulness of this construct in future drug discovery efforts aimed at specific US28 conformations. The new scaffolds identified herein represent valuable starting points for the generation of novel anti-HCMV therapies targeting the virus-encoded chemokine receptor US28 in a conformational-selective manne

Molecular dynamics-guided discovery of an ago-allosteric modulator for GPR40/FFAR1

The long-chain fatty acid receptor FFAR1/GPR40 binds agonists in both an interhelical site between the extracellular segments of transmembrane helix (TM)-III and TM-IV and a lipid-exposed groove between the intracellular segments of these helices. Molecular dynamics simulations of FFAR1 with agonist removed demonstrated a major rearrangement of the polar and charged anchor point residues for the carboxylic acid moiety of the agonist in the interhelical site, which was associated with closure of a neighboring, solvent-exposed pocket between the extracellular poles of TM-I, TM-II, and TM-VII. A synthetic compound designed to bind in this pocket, and thereby prevent its closure, was identified through structure-based virtual screening and shown to function both as an agonist and as an allosteric modulator of receptor activation. This discovery of an allosteric agonist for a previously unexploited, dynamic pocket in FFAR1 demonstrates both the power of including molecular dynamics in the drug discovery process and that this specific, clinically proven, but difficult, antidiabetes target can be addressed by chemotypes different from existing ligands