scholarly journals Geometric Analysis of Alloreactive HLAα-Helices

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Reiner Ribarics ◽  
Rudolf Karch ◽  
Nevena Ilieva ◽  
Wolfgang Schreiner
Keyword(s):  
Molecular Dynamics ◽  
T Cells ◽  
Dynamic Properties ◽  
Peptide Binding ◽  
Geometric Analysis ◽  
Md Simulations ◽  
Binding Region ◽  
Functional Elements ◽  
Mhc Molecules ◽  
Spline Models

Molecular dynamics (MD) is a valuable tool for the investigation of functional elements in biomolecules, providing information on dynamic properties and processes. Previous work by our group has characterized static geometric properties of the two MHCα-helices comprising the peptide binding region recognized by T cells. We build upon this work and used several spline models to approximate the overall shape of MHCα-helices. We applied this technique to a series of MD simulations of alloreactive MHC molecules that allowed us to capture the dynamics of MHCα-helices’ steric configurations. Here, we discuss the variability of spline models underlying the geometric analysis with varying polynomial degrees of the splines.

scholarly journals Influence on ferric chloride aqueous solution caused by external electrostatic field: a molecular dynamics simulation study

RSC Advances ◽  
2018 ◽  
Vol 8 (68) ◽  
pp. 38706-38714 ◽  
Author(s):  
Shi Zhibo ◽  
Li Liyi ◽  
Han Yong ◽  
Bai Jie
Keyword(s):  
Molecular Dynamics ◽  
Aqueous Solution ◽  
Molecular Dynamics Simulation ◽  
Ferric Chloride ◽  
Electrostatic Field ◽  
Simulation Study ◽  
Dynamic Properties ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Electrostatic Fields

A detailed analysis of structural properties and dynamic properties of ferric chloride aqueous solution under external electrostatic fields with different intensities was performed by molecular dynamics (MD) simulations.

scholarly journals Mechanistic picture for chemo-mechanical couplings in a bacterial proton-coupled oligopeptide transporter from Streptococcus thermophilus

2020 ◽  
Author(s):  
Kalyan Immadisetty ◽  
Mahmoud Moradi
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Proton Transport ◽  
Structural Changes ◽  
Streptococcus Thermophilus ◽  
Md Simulations ◽  
Electrochemical Gradient ◽  
Binding Region ◽  
Conformational Switch ◽  
Sequence Identity

AbstractProton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemo-mechanical couplings involved in substrate/proton transport and protein structural changes is missing. We therefore performed microsecond-level molecular dynamics (MD) simulations of bacterial POT transporter PepTSt, which shares ~80% sequence identity with the human POT, PepT1, in the substrate binding region. Three different conformational states of PepTSt were simulated including, (i) occluded, apo, (ii) inward-facing, apo, and (iii) inward-facingoccluded, Leu-Ala bound. We propose that the interaction of R33 with E299 and E300 acts as a conformational switch (i.e., to trigger the conformational change from an inward-to outward-facing state) in the substrate transport. Additionally, E299 and E400 should disengage from interacting with the substrate either through protonation or through co-ordination with a cation for the substrate to get transported.

scholarly journals Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2

2020 ◽  
Author(s):  
Gard Nelson ◽  
Oleksandr Buzko ◽  
Aaron Bassett ◽  
Patricia R Spilman ◽  
Kayvan Niazi ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Receptor Binding Domain ◽  
Binding Region ◽  
Angiotensin Converting Enzyme 2 ◽  
Molecular Binding ◽  
Relative Affinity ◽  
Therapeutic Development

The Receptor Binding Domain (RBD) of the SARS-CoV-2 surface spike (S) protein interacts with host angiotensin converting enzyme 2 (ACE2) to gain entry to host cells and initiate infection 1-3. Detailed, accurate understanding of key interactions between S RBD and ACE2 provides critical information that may be leveraged in the development of strategies for the prevention and treatment of COVID-19. Utilizing the published sequences and cryo-EM structures of both the viral S RBD and ACE2 4,5, we performed in silico molecular dynamics (MD) simulations of free S RBD and of its interaction with ACE2 over the exceptionally long durations of 2.9 and 2 milliseconds, respectively, to elucidate the nature and relative affinity of S RBD surface residues for the ACE2 binding region. Our findings reveal that free S RBD has assumed an optimized ACE2 binding-ready conformation, incurring little entropic penalty for binding, an evolutionary adaptation that contributes to its high affinity for the receptor 6. We further identified high probability molecular binding interactions that inform both vaccine design and therapeutic development, which may include recombinant ACE2-based spike decoys 7 and/or allosteric S RBD-ACE2 binding inhibitors 8,9 to prevent or arrest infection and thus disease.

Charge Transfer and Polarisability in Ionic Liquids

2021 ◽  
Author(s):  
Frederik Philippi ◽  
Kateryna Goloviznina ◽  
Zheng Gong ◽  
Sascha Gehrke ◽  
Barbara Kirchner ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Ionic Liquids ◽  
Charge Transfer ◽  
Dynamic Properties ◽  
Md Simulations ◽  
Classical Molecular Dynamics

The practical use of ionic liquids (ILs) is benefiting from a growing understanding of the underpinning structural and dynamic properties, facilitated through classical molecular dynamics (MD) simulations. The predictive and...

scholarly journals Fine-tuning of the AMBER RNA Force Field with a New Term Adjusting Interactions of Terminal Nucleotides

2020 ◽  
Author(s):  
Vojtěch Mlýnský ◽  
Petra Kührová ◽  
Tomáš Kühr ◽  
Michal Otyepka ◽  
Giovanni Bussi ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
State Of The Art ◽  
Dynamic Properties ◽  
Md Simulations ◽  
Experimental Methods ◽  
Fine Tuning ◽  
Enhanced Sampling ◽  
Structural Dynamic ◽  
Nmr Data

ABSTRACTDetermination of RNA structural-dynamic properties is challenging for experimental methods. Thus atomistic molecular dynamics (MD) simulations represent a helpful technique complementary to experiments. However, contemporary MD methods still suffer from limitations of force fields (ffs), including imbalances in the non-bonded ff terms. We have recently demonstrated that some improvement of state-of-the-art AMBER RNA ff can be achieved by adding a new term for H-bonding called gHBfix, which increases tuning flexibility and reduces the risk of side-effects. Still, the first gHBfix version did not fully correct simulations of short RNA tetranucleotides (TNs). TNs are key benchmark systems due to availability of unique NMR data, although giving too much weight on improving TN simulations can easily lead to over-fitting to A-form RNA. Here we combine the gHBfix version with another term called tHBfix, which separately treats H-bond interactions formed by terminal nucleotides. This allows to refine simulations of RNA TNs without affecting simulations of other RNAs. The approach is in line with adopted strategy of current RNA ffs, where the terminal nucleotides possess different parameters for the terminal atoms than the internal nucleotides. The combination of gHBfix with tHBfix significantly improves the behavior of RNA TNs during well-converged enhanced-sampling simulations. TNs mostly populate canonical A-form like states while spurious intercalated structures are largely suppressed. Still, simulations of r(AAAA) and r(UUUU) TNs show some residual discrepancies with the primary NMR data which suggests that future tuning of some other ff terms might be useful.

scholarly journals Effects of Force Fields on the Conformational and Dynamic Properties of Amyloid β(1-40) Dimer Explored by Replica Exchange Molecular Dynamics Simulations

2017 ◽  
Author(s):  
Charles R. Watts ◽  
Andrew Gregory ◽  
Cole Frisbie ◽  
Sándor Lovas
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Force Fields ◽  
Dynamic Properties ◽  
Amyloid Β ◽  
Md Simulations ◽  
Conformational Space ◽  
Random Coil ◽  
Replica Exchange ◽  
Β Sheet

AbstractAlzheimer’s disease is histologically marked by fibrils of Amyloid beta (Aβ) peptide within the extracellular matrix. Fibrils themselves are benign compared to the cytotoxicity of the oligomers and pre-fibrillary aggregates. The conformational space and structural ensembles of Aβ peptides and their oligomers in solution are inherently disordered and proven to be challenging to study. Optimum force field selection for molecular dynamics (MD) simulations and the biophysical relevance of results are still unknown. We compared the conformational space of the Aβ(1–40) dimers by 300 ns replica exchange MD simulations at physiological temperature (310 K) using: the AMBER-ff99sb-ILDN, AMBER-ff99sb*-ILDN, AMBER-ff99sb-NMR, and CHARMM22* force fields. Statistical comparisons of simulation results to experimental data and previously published simulations utilizing the CHARMM22* and CHARMM36 force fields were performed. All force fields yield sampled ensembles of conformations with collision cross sectional areas for the dimer that are statistically significantly larger than experimental results. All force fields, with the exception of AMBER-ff99sb-ILDN (8.8±6.4%) and CHARMM36 (2.7±4.2%), tend to overestimate the α-helical content compared to experimental CD (5.3±5.2%). Using the AMBER-ff99sb-NMR force field resulted in the greatest degree of variance (41.3±12.9%). Except for the AMBER-ff99sb-NMR force field, the others tended to under estimate the expected amount of β-sheet and over estimate the amount of turn/bend/random coil conformations. All force fields, with the exception AMBER-ff99sb-NMR, reproduce a theoretically expected β-sheet-turn-β-sheet conformational motif, however, only the CHARMM22* and CHARMM36 force fields yield results compatible with collapse of the central and C-terminal hydrophobic cores from residues 17-21 and 30-36. Although analyses of essential subspace sampling showed only minor variations between force fields, secondary structures of lowest energy conformers are different.

scholarly journals Dynamic and Static Properties of Aqueous NaCl Solutions at 25°C as a Function of NaCl Concentration: A Molecular Dynamics Simulation Study

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Song Hi Lee
Keyword(s):  
Molecular Dynamics ◽  
Radial Distribution ◽  
Dynamic Properties ◽  
Md Simulations ◽  
Distribution Functions ◽  
Molar Conductivity ◽  
Dynamics Simulation ◽  
Radial Distribution Functions ◽  
Deep Minimum ◽  
Nacl Concentration

We present the result of molecular dynamics (MD) simulations to calculate the molar conductivity Λ m =   λ N a + +   λ C l − of NaCl in SPC/E water at 25°C as a function of NaCl concentration (c) using Ewald sums employing a velocity Verlet algorithm. It is found that the MD result for Λm with Ewald sum parameter κ = 0.10 Å−1 gives the closest one to the experimental data and that the obtained radial distribution functions g i i (r) with κ = 0.10 Å−1 show a dramatic change with a very deep minimum of g NaCl (r) and, as a result, sharp maxima of g NaNa (r) and g ClCl (r) at the distance 9.95 Å, which indicates a characteristic of ionic atmosphere, the basis of the Debye–Hückel theory of ionic solutions. The static and dynamic properties of NaCl (aq) solutions are analyzed in terms of radial distribution functions, hydration numbers, coordination numbers around Na+ and Cl−, residence times of water around Na+ and Cl−, water diffusion, and ion-ion electrostatic energies to explain the behavior of the molar conductivity Λm of NaCl obtained from our MD simulations.

Efficient Treatment of Fixed and Induced Dipolar Interactions

2000 ◽  
Vol 653 ◽  
Author(s):  
Celeste Sagui ◽  
Thoma Darden
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Lagrangian Formalism ◽  
Dipolar Interactions ◽  
Time Step ◽  
Efficient Treatment ◽  
Particle Mesh Ewald ◽  
Fixed Charges ◽  
Self Consistency ◽  
Induced Dipoles

AbstractFixed and induced point dipoles have been implemented in the Ewald and Particle-Mesh Ewald (PME) formalisms. During molecular dynamics (MD) the induced dipoles can be propagated along with the atomic positions either by interation to self-consistency at each time step, or by a Car-Parrinello (CP) technique using an extended Lagrangian formalism. The use of PME for electrostatics of fixed charges and induced dipoles together with a CP treatment of dipole propagation in MD simulations leads to a cost overhead of only 33% above that of MD simulations using standard PME with fixed charges, allowing the study of polarizability in largemacromolecular systems.

MHC Sınıf I ve MHC Sınıf II Gen Düzenlenmesi

2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Gene Regulation ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Regulation Mechanisms

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription

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