Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is ...due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion.
In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied.
Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes.
Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics.
Display omitted
•Insufficient conformational sampling often limits molecular dynamics applications.•REMD and metadynamics allow a broader exploration of the energy surface.•GSA can be employed for large flexible macromolecular complexes.•GSA shows that a flexible linker in the cellulosome allows two preferential conformations.
The results of dielectric relaxation spectroscopy of the chiral liquid crystal 4′-butyl-4-(2-methylbutoxy)azoxybenzene in the crystal phase are presented. The scaling procedure showed complex ...molecular dynamics and allows one to decompose the observed relaxation process into two closely located relaxation processes around the short molecular axis. Temperature dependences of relaxation times characterizing flip-flop motions (rotation around the short molecular axis) and rotation around the long molecular axis are of the Arrhenius type.
Lithium–sulfur batteries have ultra–high energy density and are considered to be one of the most promising energy storage systems among all battery systems. However, due to various thorny problems, ...their commercial production has not yet been realized. The current experimental research normally lacks a systematic investigation into the conversion mechanism of the sulfur cathode from the electronic structure level. Actually, there is still a lack of powerful theoretical guidance for the design of high–performance Li–S batteries and the selection of modified materials still seems blind. In this article, with the chelated Fe‐polyvinyl pyrrolidone as the precursor, a series of Fe–based materials (e.g., Fe3O4@C, FeS@C, Fe3N@C) are synthesized as modified layers for battery separators, and the performance differences between them are systematically studied. It is found that the d–p band center model developed based on the d band center can reasonably combine the reaction potential of Li2S4 and performance differences. Simultaneously, the interaction between Li2S6 and the adsorption interface is simulated by ab initio molecular dynamics. This current work sheds light on promising material design for superior Li–S batteries both from a theoretical and experimental perspective.
Fe–based functional materials are adopted to modify separators for Li–S batteries, and it is found that the d–p band center model based on the d band center can reasonably combine the reaction potential of Li2S4 and performance differences. With the help of ab initio molecular dynamics, the catalysis process of Fe3C at the molecular level is demonstrated.
Micro-Exon Genes are a widespread class of genes known for their high variability, widespread in the genome of parasitic trematodes such as Schistosoma mansoni. In this study, we present a strategy ...that allowed us to solve the structures of three alternatively spliced isoforms from the Schistoma mansoni MEG 2.1 family for the first time. All isoforms are hydrophobic, intrinsically disordered, and recalcitrant to be expressed in high yield in heterologous hosts. We resorted to the chemical synthesis of shorter pieces, before reconstructing the entire sequence. Here, we show that isoform 1 partially folds in a-helix in the presence of trifluoroethanol while isoform 2 features two rigid elbows, that maintain the peptide as disordered, preventing any structuring. Finally, isoform 3 is dominated by the signal peptide, which folds into a-helix. We demonstrated that combining biophysical techniques, like circular dichroism and nuclear magnetic resonance at natural abundance, with in silico molecular dynamics simulation for isoform 1 only, was the key to solve the structure of MEG 2.1. Our results provide a crucial piece to the puzzle of this elusive and highly variable class of proteins.
The application of asphalt materials in pavement engineering has been increasingly widespread and sophisticated over the past several decades. Variations in the properties of asphalt binder during ...mixing, transportation, and paving can affect the performance of asphalt pavement. However, the asphalt material is a non-homogeneous and complex organic substance, consisting of various molecules with widely various molecular weights, elemental compositions, and structures. This complexity leads to difficulties for researchers to clearly and immediately understand the properties of asphalt materials and their variations. The multi-scale research approach combines macroscopic experimental data and microscopic simulation results from a practical engineering perspective. It helps to improve the understanding of asphalt materials. The molecular dynamics (MD) simulation proposes a corresponding molecular model of asphalt material based on experimental data, and the simulation algorithm is able to derive properties similar to those of real asphalt. This paper provides a comprehensive review of the current studies on MD simulation of asphalt materials, including modeling, properties, and multi-scale analysis. As a key part of the computational simulation, this paper discusses the typical asphalt binder and asphalt-aggregate interface models constructed by different groups, and also presents their differences from real samples and their feasibility based on fundamental properties. After the introduction of molecular models, the extensive work made by researchers based on molecular models is categorically reviewed and discussed. The strengths and weaknesses of MD simulation methods in the study of asphalt materials are also summarized in order to provide the reader with a more comprehensive understanding of the relevant contents and to guide subsequent research.
Display omitted
•The advantages and disadvantages of the Molecular Dynamics method were demonstrated.•A comprehensive discussion of the Molecular Dynamics Method in asphalt material was explored.•Many research directions of the Molecular Dynamics Method in asphalt material were discussed and guided.
How cholesterol stiffens unsaturated lipid membranes Chakraborty, Saptarshi; Doktorova, Milka; Molugu, Trivikram R. ...
Proceedings of the National Academy of Sciences - PNAS,
09/2020, Volume:
117, Issue:
36
Journal Article
Peer reviewed
Open access
Cholesterol is an integral component of eukaryotic cell membranes and a key molecule in controlling membrane fluidity, organization, and other physicochemical parameters. It also plays a regulatory ...function in antibiotic drug resistance and the immune response of cells against viruses, by stabilizing the membrane against structural damage. While it iswell understood that, structurally, cholesterol exhibits a densification effect on fluid lipid membranes, its effects on membrane bending rigidity are assumed to be nonuniversal; i.e., cholesterol stiffens saturated lipid membranes, but has no stiffening effect on membranes populated by unsaturated lipids, such as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). This observation presents a clear challenge to structure–property relationships and to our understanding of cholesterol-mediated biological functions. Here, using a comprehensive approach—combining neutron spin-echo (NSE) spectroscopy, solid-state deuterium NMR (²H NMR) spectroscopy, and molecular dynamics (MD) simulations—we report that cholesterol locally increases the bending rigidity of DOPC membranes, similar to saturated membranes, by increasing the bilayer’s packing density. All three techniques, inherently sensitive to mesoscale bending fluctuations, show up to a threefold increase in effective bending rigidity with increasing cholesterol content approaching a mole fraction of 50%. Our observations are in good agreement with the known effects of cholesterol on the area-compressibility modulus and membrane structure, reaffirming membrane structure–property relationships. The current findings point to a scale-dependent manifestation of membrane properties, highlighting the need to reassess cholesterol’s role in controlling membrane bending rigidity over mesoscopic length and time scales of important biological functions, such as viral budding and lipid–protein interactions.
The hydrogen storage behaviors of the nitride-based MXenes Ti.sub.2N have been investigated by performing density functional calculations. It is observed that H.sub.2-molecules could be adsorbed on ...and desorbed from Ti.sub.2N monolayer with suitable adsorption strength under ambient conditions. Moreover, the stability and hydrogen adsorption behaviors are analyzed by computing adsorption energy, charge population and ab initio molecular dynamic simulations. The Kubas-type interaction of the H.sub.2-molecules with Ti.sub.2N monolayer is investigated according to the charge transfer and electronic projected density of states. Specifically, it is found that the maximum hydrogen storage capacity of Ti.sub.2N reaches up to 8.555 wt%, in which the reversible hydrogen storage capacity is of 3.422 wt%. In addition, OH-group-decorated Ti.sub.2N has great advantages on hydrogen storage, and the reversible hydrogen storage capacity is of 2.656 wt%. Therefore, the 2D Ti.sub.2N MXenes are expected for a potential candidate as reversible hydrogen storage materials under ambient conditions.
A systematic method to calculate anharmonic force constants of crystals is presented. The method employs the direct-method approach, where anharmonic force constants are extracted from the trajectory ...of first-principles molecular dynamics simulations at high temperature. The method is applied to Si where accurate cubic and quartic force constants are obtained. We observe that higher-order correction is crucial to obtain accurate force constants from the trajectory with large atomic displacements. The calculated harmonic and anharmonic force constants are, then, combined with the Boltzmann transport equation (BTE) and non-equilibrium molecular dynamics (NEMD) methods in calculating the thermal conductivity. The BTE approach successfully predicts the lattice thermal conductivity of bulk Si, whereas NEMD shows considerable underestimates. To evaluate the linear extrapolation method employed in NEMD to estimate bulk values, we analyze the size dependence in NEMD based on BTE calculations. We observe strong nonlinearity in the size dependence of NEMD in Si, which can be ascribed to acoustic phonons having long mean-free-paths and carrying considerable heat. Subsequently, we also apply the whole method to a thermoelectric material Mg2Si and demonstrate the reliability of the NEMD method for systems with low thermal conductivities.
Several hypotheses have been proposed to explain the strong association of HLA-B27 with a group of inflammatory arthritic disorders, known as the spondyloarthropathies. According to one such theory, ...HLA-B27 participates in disease pathogenesis through its enhanced ability to form cysteine-mediated heavy chain-dimer populations. However, none of the theories provide any scope to explain the differential disease association of the different subtypes of HLA-B27. We have hypothesized a detailed novel molecular mechanism based on phenomenological arguments supported by molecular modeling and molecular dynamics simulations for the misfolding of B27 chains, resulting in formation of high molecular weight (HMW) aggregates, in the absence of beta-2 m and peptide. According to this hypothesis, a helix-unfolding transition allows a part of the B27 chain (identical in sequence to a known B27 ligand) to become free to loop around and bind to a structurally distorted peptide-binding cleft, in the same B27 molecule (auto-display) or in a neighboring molecule (cross-auto display). We have studied such HMW forms of B27, through biophysical and biochemical investigations, and further, using various cysteine mutants of B27, we have been able to investigate the nature of misfolded B27 in the disease associated (B2705) vs the non-disease-associated (B2709) subtypes, to obtain some direct, rather than circumstantial evidence, both, for cross-auto display and the role of such display in pathogenesis.
PDF
