Simulating Peptide Monolayer Formation: GnRH-I on Silica

Molecular dynamics (MD) simulations can provide a detailed view of molecule behaviour at an atomic level, which can be useful when attempting to interpret experiments or design new systems. The decapeptide gonadotrophin-releasing hormone I (GnRH-I) is known to control fertility in mammals for both sexes. It was previously shown that inoculation with silica nanoparticles (SiNPs) coated with GnRH-I makes an effective anti-fertility vaccine due to how the peptide adsorbs to the nanoparticle and is presented to the immune system. In this paper, we develop and employ a protocol to simulate the development of a GnRH-I peptide adlayer by allowing peptides to diffuse and adsorb in a staged series of trajectories. The peptides start the simulation in an immobile state in solution above the model silica surface, and are then released sequentially. This facile approach allows the adlayer to develop in a natural manner and appears to be quite versatile. We find that the GnRH-I adlayer tends to be sparse, with electrostatics dominating the interactions. The peptides are collapsed to the surface and are seemingly free to interact with additional solutes, supporting the interpretations of the GNRH-I/SiNP vaccine system.

Download Full-text

Simulation of Thermal Stability and Friction: A Lubricant Confined Between Monolayers of Wear Inhibitors on Iron Oxide

MRS Proceedings ◽

10.1557/proc-543-79 ◽

1998 ◽

Vol 543 ◽

Cited By ~ 2

Author(s):

T. Çağin ◽

Y. Zhou ◽

E. S. Yamaguchi ◽

R. Frazier ◽

A. Ho ◽

...

Keyword(s):

Molecular Dynamics ◽

Thermal Stability ◽

Quantum Chemical ◽

Md Simulations ◽

Atomic Level ◽

The Self ◽

Self Assembled Monolayer ◽

Thermal Stabilities ◽

Frictional Forces ◽

Thermal Stability Of

AbstractTo understand antiwear phenomena in motor engines at the atomic level and provide evidence inselecting future ashless wear inhibitors, we studied the thermal stability of the self-assembled monolayer(SAM) model for dithiophosphate (DTP) and dithiocarbamate (DTC) molecules on the iron oxidesurface using molecular dynamics. The interactions for DTP, DTC and Fe2O3 are evaluated based on aforce field derived from fitting to ab initio quantum chemical calculations of dimethyl DTP (and DTC)and Fe(OH)2(H2O)2-DTP (DTC) clusters. MD simulations at constant-NPT are conducted to assesrelative thermal stabilities of the DTP and DTC with different pendant groups (n-propyl, i-propyl, npentyl.and i-pentyl). To investigate frictional process, we employ a steady state MD method, in whichone of the Fe2O3 slabs maintained at a constant linear velocity. We obtain the time averaged normaland frictional forces from the interatomic forces. Then, we calculated the friction coefficient at theinterface between SAMs of DTP and the confined lubricant, hexadecane, to assess the shear stability ofDTPs with different pendant groups.

Download Full-text

Structure and Dynamics of Glycosphingolipids in Lipid Bilayers: Insights from Molecular Dynamics Simulations

International Journal of Carbohydrate Chemistry ◽

10.1155/2011/950256 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Ronak Y. Patel ◽

Petety V. Balaji

Keyword(s):

Molecular Dynamics ◽

Lipid Bilayers ◽

Membrane Structure ◽

Lipid Membrane ◽

Biological Membranes ◽

Md Simulations ◽

Atomic Level ◽

Structure And Dynamics ◽

Hydrogen Bonding Interactions ◽

Dynamics Simulations

Glycolipids are important constituents of biological membranes, and understanding their structure and dynamics in lipid bilayers provides insights into their physiological and pathological roles. Experimental techniques have provided details into their behavior at model and biological membranes; however, computer simulations are needed to gain atomic level insights. This paper summarizes the insights obtained from MD simulations into the conformational and orientational dynamics of glycosphingolipids and their exposure, hydration, and hydrogen-bonding interactions in membrane environment. The organization of glycosphingolipids in raft-like membranes and their modulation of lipid membrane structure are also reviewed.

Download Full-text

Molecular motions in a fluxional (η6-indenyl)tricarbonylchromium hemichelate: a density functional theory molecular dynamics study

Dalton Transactions ◽

10.1039/c8dt01779d ◽

2018 ◽

Vol 47 (27) ◽

pp. 8906-8920 ◽

Cited By ~ 2

Author(s):

Nicolas Sieffert

Keyword(s):

Molecular Dynamics ◽

Density Functional Theory ◽

Density Functional ◽

Md Simulations ◽

Atomic Level ◽

Molecular Motions ◽

Comprehensive Understanding ◽

Intramolecular Dynamics ◽

Functional Theory

DFT-MD simulations provided atomic-level insights into the intramolecular dynamics of a highly fluxional Pd(ii) hemichelate and a comprehensive understanding of the thermodynamics and the kinetics associated with each motion.

Download Full-text

Atomic Level Insight into Wetting and Structure of Ag Droplet on Graphene Coated Copper Substrate—Molecular Dynamics versus Experiment

Nanomaterials ◽

10.3390/nano11061465 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1465

Author(s):

Aleksandra Drewienkiewicz ◽

Arkadiusz Żydek ◽

Marcela E. Trybula ◽

Janusz Pstruś

Keyword(s):

Molecular Dynamics ◽

Copper Substrate ◽

Md Simulations ◽

Atomic Level ◽

Wetting Behavior ◽

Graphene Layers ◽

Metal Interactions ◽

Metal Metal ◽

Perfect Graphene ◽

Pure Cu

Understanding the atomic-level phenomena occurring upon the wetting of graphene-coated Cu with liquid Ag is pivotal for the description of the wetting phenomenon and the role of graphene as a diffusion barrier. We have performed molecular dynamics (MD) simulations and confronted with our present experimental results to characterize wetting behavior of graphene coated Cu surfaces. Perfect and defected graphene layers covering Cu surface were wetted with liquid Ag droplet at 1273 K. Structural and topological aspects are discussed to characterize structure of the liquid Ag droplet and a product of wetting reaction occurring on Cu/Gn and Cu/Gndef substrates, also including perfect graphene layer and a pure Cu surface. The obtained results reveal the importance of defects in graphene structure, which play a key role in wetting mechanism and the formation of AgCu alloy. As a consequence, we observe a change of the wetting behavior and topology of both bulk and adsorbed Ag atoms by using Voronoi analysis (VA). Despite the differences in time scale, atomistic simulations allowed us to catch the early stages of wetting, which are important for explaining the final stage of wetting delivered from experiment. Our findings reveal also graphene translucency to metal-metal interactions, observed in previous papers.

Download Full-text

Molecular Dynamics to Predict Cryo-EM: Capturing Transitions and Short-Lived Conformational States of Biomolecules

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.641208 ◽

2021 ◽

Vol 8 ◽

Author(s):

Łukasz Nierzwicki ◽

Giulia Palermo

Keyword(s):

Molecular Dynamics ◽

Md Simulations ◽

Atomic Level ◽

Conformational States ◽

Variable Regions ◽

Biologically Relevant ◽

Active Structure ◽

Conformational Variability ◽

Challenges And Opportunities ◽

Catalytically Active

Single-particle cryogenic electron microscopy (cryo-EM) has revolutionized the field of the structural biology, providing an access to the atomic resolution structures of large biomolecular complexes in their near-native environment. Today’s cryo-EM maps can frequently reach the atomic-level resolution, while often containing a range of resolutions, with conformationally variable regions obtained at 6 Å or worse. Low resolution density maps obtained for protein flexible domains, as well as the ensemble of coexisting conformational states arising from cryo-EM, poses new challenges and opportunities for Molecular Dynamics (MD) simulations. With the ability to describe the biomolecular dynamics at the atomic level, MD can extend the capabilities of cryo-EM, capturing the conformational variability and predicting biologically relevant short-lived conformational states. Here, we report about the state-of-the-art MD procedures that are currently used to refine, reconstruct and interpret cryo-EM maps. We show the capability of MD to predict short-lived conformational states, finding remarkable confirmation by cryo-EM structures subsequently solved. This has been the case of the CRISPR-Cas9 genome editing machinery, whose catalytically active structure has been predicted through both long-time scale MD and enhanced sampling techniques 2 years earlier than cryo-EM. In summary, this contribution remarks the ability of MD to complement cryo-EM, describing conformational landscapes and relating structural transitions to function, ultimately discerning relevant short-lived conformational states and providing mechanistic knowledge of biological function.

Download Full-text

On the equivalence of the two foundational formulations for atomistic flux in inhomogeneous transport processes

Proceedings of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rspa.2018.0688 ◽

2019 ◽

Vol 475 (2223) ◽

pp. 20180688 ◽

Cited By ~ 3

Author(s):

Adrian Diaz ◽

Denis Davydov ◽

Youping Chen

Keyword(s):

Molecular Dynamics ◽

Statistical Mechanics ◽

Energy Transport ◽

Md Simulations ◽

Atomic Level ◽

Transport Processes ◽

Spatial Averaging ◽

Dirac Delta ◽

Pair Density ◽

Different Types

Although there are numerous formulae for atomic-level fluxes, they are expressed either in terms of a singlet density, resulting from Irving and Kirkwood's statistical mechanics formulation of hydrodynamical equations, or a pair density, proposed in kinetic theories of transport processes. Flux formulae using singlet density have been further developed and widely implemented in molecular dynamics (MD) simulations by either replacing the Dirac delta with a volumetric averaging function or performing a surface average of the flux operators. Pair density-based flux formulae have also been further developed by using spatial-averaging kernels; these formulae, however, have rarely been implemented or used in modern MD. In this work, distributional calculus is used to reformulate the fluxes in momentum and energy transport processes. The formulation results demonstrate that these two types of existing flux formulae are mathematically equivalent when expressed with the Dirac delta. The lasting confusion regarding these two different types of flux formulae from two different formalisms is thus resolved.

Download Full-text

Efficient Treatment of Fixed and Induced Dipolar Interactions

MRS Proceedings ◽

10.1557/proc-653-z7.22 ◽

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.

Download Full-text

Split the Charge Difference in Two! a Rule of Thumb for Adding Proper Amounts of Ions in MD Simulations

10.26434/chemrxiv.9783155.v2 ◽

2020 ◽

Author(s):

Matías R. Machado ◽

Sergio Pantano

Keyword(s):

Molecular Dynamics ◽

Ionic Strength ◽

Molecular Simulations ◽

Md Simulations ◽

Good Practices ◽

Rule Of Thumb ◽

Ionic Concentrations

Despite the relevance of properly setting ionic concentrations in Molecular Dynamics (MD) simulations, methods or practical rules to set ionic strength are scarce and rarely documented. Based on a recently proposed thermodynamics method we provide an accurate rule of thumb to define the electrolytic content in simulation boxes. Extending the use of good practices in setting up MD systems is promptly needed to ensure reproducibility and consistency in molecular simulations.

Download Full-text

Assessing the Antimalarial Potentials of Phytochemicals: Virtual Screening, Molecular Dynamics and In-Vitro Investigations

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180604085626 ◽

2019 ◽

Vol 16 (3) ◽

pp. 291-300

Author(s):

Saumya K. Patel ◽

Mohd Athar ◽

Prakash C. Jha ◽

Vijay M. Khedkar ◽

Yogesh Jasrai ◽

...

Keyword(s):

Molecular Dynamics ◽

Structural Integrity ◽

Md Simulations ◽

Tylophora Indica ◽

Multidrug Resistance Protein 1 ◽

Receptor Complexes ◽

Resistance Protein ◽

Dynamics Simulations ◽

Stable Trajectory

Background: Combined in-silico and in-vitro approaches were adopted to investigate the antiplasmodial activity of Catharanthus roseus and Tylophora indica plant extracts as well as their isolated components (vinblastine, vincristine and tylophorine). Methods: We employed molecular docking to prioritize phytochemicals from a library of 26 compounds against Plasmodium falciparum multidrug-resistance protein 1 (PfMDR1). Furthermore, Molecular Dynamics (MD) simulations were performed for a duration of 10 ns to estimate the dynamical structural integrity of ligand-receptor complexes. Results: The retrieved bioactive compounds viz. tylophorine, vinblastin and vincristine were found to exhibit significant interacting behaviour; as validated by in-vitro studies on chloroquine sensitive (3D7) as well as chloroquine resistant (RKL9) strain. Moreover, they also displayed stable trajectory (RMSD, RMSF) and molecular properties with consistent interaction profile in molecular dynamics simulations. Conclusion: We anticipate that the retrieved phytochemicals can serve as the potential hits and presented findings would be helpful for the designing of malarial therapeutics.

Download Full-text

On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽

10.3390/polym13010099 ◽

2020 ◽

Vol 13 (1) ◽

pp. 99

Author(s):

Cristian Privat ◽

Sergio Madurga ◽

Francesc Mas ◽

Jaime Rubio-Martínez

Keyword(s):

Molecular Dynamics ◽

Amino Acids ◽

Md Simulations ◽

Point Of View ◽

Conformational Space ◽

Conformational Sampling ◽

Protonation State ◽

Constant Ph ◽

Biochemical Systems ◽

Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

Download Full-text