Step Of Molecular Dynamics Simulation Research Articles

Computational prediction method to decipher receptor-glycoligand interactions in plant immunity.

SUMMARYMicrobial and plant cell walls have been selected by the plant immune system as a source of microbe‐ and plant damage‐associated molecular patterns (MAMPs/DAMPs) that are perceived by extracellular ectodomains (ECDs) of plant pattern recognition receptors (PRRs) triggering immune responses. From the vast number of ligands that PRRs can bind, those composed of carbohydrate moieties are poorly studied, and only a handful of PRR/glycan pairs have been determined. Here we present a computational screening method, based on the first step of molecular dynamics simulation, that is able to predict putative ECD‐PRR/glycan interactions. This method has been developed and optimized with Arabidopsis LysM‐PRR members CERK1 and LYK4, which are involved in the perception of fungal MAMPs, chitohexaose (1,4‐β‐d‐(GlcNAc)6) and laminarihexaose (1,3‐β‐d‐(Glc)6). Our in silico results predicted CERK1 interactions with 1,4‐β‐d‐(GlcNAc)6 whilst discarding its direct binding by LYK4. In contrast, no direct interaction between CERK1/laminarihexaose was predicted by the model despite CERK1 being required for laminarihexaose immune activation, suggesting that CERK1 may act as a co‐receptor for its recognition. These in silico results were validated by isothermal titration calorimetry binding assays between these MAMPs and recombinant ECDs‐LysM‐PRRs. The robustness of the developed computational screening method was further validated by predicting that CERK1 does not bind the DAMP 1,4‐β‐d‐(Glc)6 (cellohexaose), and then probing that immune responses triggered by this DAMP were not impaired in the Arabidopsis cerk1 mutant. The computational predictive glycan/PRR binding method developed here might accelerate the discovery of protein–glycan interactions and provide information on immune responses activated by glycoligands.

Ultrafast Formation of the Charge Transfer State of Prodan Reveals Unique Aspects of the Chromophore Environment.

Lipophilic dyes such as laurdan and prodan are widely used in membrane biology due to a strong bathochromic shift in emission that reports the structural parameters of the membrane such as area per molecule. Disentangling of the factors which control the spectral shift is complicated by the stabilization of a charge-transfer-like excitation of the dye in polar environments. Predicting the emission therefore requires modeling both the relaxation of the environment and the corresponding evolution of the excited state. Here, an approach is presented in which (i) the local environment is sampled by a classical molecular dynamics (MD) simulation of the dye and solvent, (ii) the electronically excited state of prodan upon light absorption is predicted by numerical quantum mechanics (QM), (iii) the iterative relaxation of the environment around the excited dye by MD coupled with the evolution of the excited state is performed, and (iv) the emission properties are predicted by QM. The QM steps are computed using the many-body Green's function in the GW approximation and the Bethe-Salpeter equation with the environment modeled as fixed point charges, sampled in the MD simulation steps. The comparison to ultrafast time-resolved transient absorption measurements demonstrates that the iterative molecular mechanics (MM)/QM approach agrees quantitatively with both the polarity-dependent shift in emission and the time scale over which the charge transfer state is stabilized. Together the simulations and experimental measurements suggest that the evolution into the charge transfer state is slower in amphiphilic solvents.

Predicting Spectral Properties of Polarity Sensitive Dyes with QM/MM Simulation

Polarity sensitive, lipophilic dyes such as Laurdan report lipid packing in biomembranes, as the emission spectrum is red shifted in more polar environments. In simple membranes, the dye is more accessible to solvent in more disordered membranes, and the spectral shift is well-explained by dipolar relaxation of the solvent. However, in more complex systems other factors may contribute, especially hydrogen bonding between the environment and the chromophore. Disentangling the factors which control the spectral shift is complicated by the fact that polar environments likely stabilize a charge transfer-like state, and so predicting the emission requires accurate modeling of the relaxation of the environment around the excited state. An approach has been developed in which (i) the local environment is sampled by classical molecular dynamics (MD) simulation of the dye; (ii) prediction of the absorption and excited state by numerical quantum mechanics (QM); (iii) parameterization of an excited state MD model (iv) relaxation of the environment around the excited state by MD; (v) prediction of the emission by QM. The QM steps are computed using GW-BSE (as implemented in Versatile Object-oriented Toolkit for Coarse-graining Applications: Exciton Transport Simulations (VOTCA-XTP)) with the environment modeled as fixed point charges, sampled in the MD simulation steps. Comparison to time dependent DFT shows that GW-BSE yields much more quantitative predictions for both absorption and emission, as expected for charge transfer states, because GW more accurately captures the effective electron-hole interactions following an excitation. The results reveal the mechanisms responsible for the spectral shift of Laurdan, and map an approach for similar applications to other polarity sensitive probes.

Salt Effect on Osmotic Pressure of Polyelectrolyte Solutions: Simulation Study

Abstract: We present results of the hybrid Monte Carlo/molecular dynamics simulations of the osmotic pressure of salt solutions of polyelectrolytes. In our simulations, we used a coarse-grained representation of polyelectrolyte chains, counterions and salt ions. During simulation runs, we alternate Monte Carlo and molecular dynamics simulation steps. Monte Carlo steps were used to perform small ion exchange between simulation box containing salt ions (salt reservoir) and simulation box with polyelectrolyte chains, counterions and salt ions (polyelectrolyte solution). This allowed us to model Donnan equilibrium and partitioning of salt and counterions across membrane impermeable to polyelectrolyte chains. Our simulations have shown that the main contribution to the system osmotic pressure is due to salt ions and osmotically active counterions. The fraction of the condensed (osmotically inactive) counterions first increases with decreases in the solution ionic strength then it saturates. The reduced value of the system osmotic coefficient is a universal function of the ratio of the concentration of osmotically active counterions and salt concentration in salt reservoir. Simulation results are in a very good agreement with osmotic pressure measurements in sodium polystyrene sulfonate, DNA, polyacrylic acid, sodium polyanetholesulfonic acid, polyvinylbenzoic acid, and polydiallyldimethylammonium chloride solutions.

Structure of the virus capsid protein VP1 of enterovirus 71 predicted by some homology modeling and molecular docking studies

The homology modeling technique has been used to construct the structure of enterovirus 71 (EV 71) capsid protein VP1. The protein is consisted of 297 amino acid residues and treated as the target. The amino acid sequence identity between the target protein and sequences of template proteins 1EAH, 1PIV, and 1D4M searched from NCBI protein BLAST and WorkBench protein tools were 38, 37, and 36%, respectively. Based on these template structures, the protein model was constructed by using the InsightII/Homology program. The protein model was briefly refined by energy minimization and molecular dynamics (MD) simulation steps. The protein model was validated using some web available servers such as ERRAT, PROCHECK, PROVE, and PROSA2003. However, an inconsistency between the docking scores and the measured activity was observed for a series of EV 71 VP1 inhibitors synthesized by Shia et al. (J Med Chem 2002, 45, 1644) and docked into the binding pocket of the protein model using the DOCK 4.0.2 program. The protein model with an EV 71 VP1 inhibitor docked and engulfed was then refined further by some MD simulation steps in the presence of water molecules. The docking scores obtained for these inhibitors after such a MD refinement were well correlated with the activities. The structure-activity relationships for the ligand-protein model system was also analyzed using the GRID-VOLSURF programs and the corresponding noncrossvalidated and crossvalidated (by leave-one-out) r2 and q2 were 0.99 and 0.61, respectively. The hydrophobic nature of the binding pocket of the protein model was also examined using the GRID21 program. The possibility of improving the potency of the current series of EV 71 VP1 inhibitors was discussed based on all the studies presented.

Molecular dynamics simulation of oxides with ionic–covalent bonds

A “semi-classical” method was developed for molecular dynamics simulation of a system with ionic–covalent bonds like silica. The ionic charges were calculated by minimization of the potential energy on each step of molecular dynamics simulation. Ionic–covalent potential was used in modeling of SiO 2 molecule, non-crystalline silica, and calcium metasilicate. The internal energy of a system includes energies of silicon ionization, affinity of oxygen to electrons, Coulomb interactions and repulsion of ions, and covalent SiO energy. Calculated properties of glassy and liquid silica and SiO 2 molecule, such as density, internal energy, compressibility, distances between ions and vibration frequencies, are close to experimental values.

Molecular dynamics simulation on phosphorus behavior at Ni grain boundary

Phosphorus is commonly regarded as a common impurity and detrimental element in most Fe-base and Ni-base alloys. To study the problem in detail, it is feasible to use computer simulation techniques, which can investigate events on a much finer space and time scale than can be reached with presently available experimental techniques. The study of fracture and embrittlement at the atomic scale often used molecular dynamics (MD) and quantum-chemical methods. The most important and difficult step of molecular dynamics simulation is the determination of interatomic potential. As the first step of studying on the behavior of phosphorus in Ni-Cr-Fe system, the goal of this paper is to study the behavior of phosphorus in Ni grain boundary.