scholarly journals Tentative Peptide‒Lipid Bilayer Models Elucidating Molecular Behaviors and Interactions Driving Passive Cellular Uptake of Collagen-Derived Small Peptides

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 710
Author(s):  
Pathomwat Wongrattanakamon ◽  
Wipawadee Yooin ◽  
Busaban Sirithunyalug ◽  
Piyarat Nimmanpipug ◽  
Supat Jiranusornkul
Keyword(s):  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Mean Square Displacement ◽  
Dynamics Simulation ◽  
Coordinate Frame ◽  
Mean Square ◽  
Binding Modes ◽  
Small Peptides ◽  
Collagen Peptides ◽  
Electron Density Profiles

Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived small peptides (Gly-Pro-Hyp, Pro-Hyp, and Gly-Hyp) interacting across a lipid bilayer (POPC model membrane) for cellular uptakes of these collagen-derived small peptides were studied using accelerated molecular dynamics simulation. The ligands were investigated for their binding modes, hydrogen bonds in each coordinate frame, and mean square displacement (MSD) in the Z direction. The lipid bilayers were evaluated for mass and electron density profiles of the lipid molecules, surface area of the head groups, and root mean square deviation (RMSD). The simulation results show that hydrogen bonding between the small collagen peptides and plasma membrane plays a significant role in their internalization. The translocation of the small collagen peptides across the cell membranes was shown. Pro-Hyp laterally condensed the membrane, resulting in an increase in the bilayer thickness and rigidity. Perception regarding molecular behaviors of collagen-derived peptides within the cell membrane, including their interactions, provides the novel design of specific bioactive collagen peptides for their applications.

Molecular dynamics simulation of aggregation of monocrystal and polycrystal copper nanoparticles

2019 ◽  
Vol 33 (16) ◽  
pp. 1950168
Author(s):  
Linxing Zhang ◽  
Guang Hong ◽  
Shouyin Cai
Keyword(s):  
Molecular Dynamics ◽  
Lattice Structure ◽  
Displacement Vector ◽  
Mean Square Displacement ◽  
Dynamics Simulation ◽  
Gyration Radius ◽  
Mean Square ◽  
Shrinkage Ratio ◽  
Lower Temperature ◽  
Dynamics Simulations

Molecular dynamics simulations were employed to investigate the aggregation of monocrystal and polycrystal nanoparticles. The lattice structure, displacement vector, potential energy, shrinkage ratio, relative gyration radius and mean square displacement of the two systems are compared. The results indicate that the aggregation of polycrystal nanoparticles is more drastic than that of monocrystal nanoparticles. Besides, the polycrystal nanoparticles are found contacted and melted at lower-temperature than that of monocrystal nanoparticles. The reason for all these phenomena is that there is additional surface energy in the grain boundary of polycrystal nanoparticles.

scholarly journals Molecular Dynamics Simulation of the Interaction Between Benzanthrone Dye and Model Lipid Membranes

2020 ◽  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Fluorescent Dyes ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Membrane Composition ◽  
Model Lipid Membranes

The benzanthrone fluorescent dyes are known as environmentally-sensitive reporters for exploring the physicochemical properties and structural alterations of lipid membranes. In the present work the 100-ns molecular dynamics simulation (MD) was used to characterize the bilayer location and the nature of interactions between the benzanthrone fluorescent dye ABM and the model lipid membranes composed of the zwitterionic lipid phosphatidylcholine (PC) and its mixtures with the anionic lipid phosphatidylglycerol (PG20) and sterol cholesterol (Chol30). The MD simulations were performed in the CHARMM36m force field using the GROMACS package. The ABM molecule, which was initially placed at a distance of 30 Å from the midplane of the lipid bilayer, after 10 ns of simulation was found to be completely incorporated into the membrane interior and remained within the lipid bilayer for the rest of the simulation time. The analysis of the MD simulation results showed that the lipid bilayer location of the benzanthrone dye ABM depends on the membrane composition, with the distance from bilayer center being gradually shifted from 0.78 nm in the neat PC bilayer to 0.95 nm and 1.5 nm in the PG- and Chol-containing membranes, respectively. In addition, the partitioning of the ABM into the neat PC bilayer was followed by the probe translocation from the outer membrane leaflet to the inner one. A separate series of MD simulations was aimed at examining the ABM influence on the lipid bilayer structure. It was found that ABM partitioning into the lipid bilayers of various composition has no significant effect on the orientation of the fatty acid chains and leads only to a small increase of the deuterium order parameter for the carbon atoms 5-to-8 in the sn-2 acyl chains of the neat PC membranes. In addition, the interaction of the ABM with the model lipid membranes caused the slight decrease of the surface area per lipid pointing to the slight increase of the packing density of lipid molecules in the presence of ABM. The results obtained provide a basis for deeper understanding of the membrane interactions of benzanthrone dyes and may be useful for the design of the novel fluorescent probes for membrane studies.

Improving Monte-Carlo and Molecular Dynamics Simulation Outcomes Using Temperature-Dependent Interaction Parameters: The Case of Pure LJ Fluid

2015 ◽  
Vol 12 (02) ◽  
pp. 1550003 ◽  
Author(s):  
Ali Kh. Al-Matar ◽  
Ahmed H. Tobgy ◽  
Ibrahim A. Suleiman ◽  
Majdi A. Al-Faiad
Keyword(s):  
Molecular Dynamics ◽  
Mean Square Displacement ◽  
Dynamics Simulation ◽  
Interaction Parameters ◽  
Mean Square ◽  
Temperature Dependent ◽  
Temperature Range ◽  
Significant Difference ◽  
Dependent Interaction ◽  
Vapor Liquid

The main proposition of this work is that introducing temperature-dependent interaction parameters (TDIP) instead of using temperature-independent interaction parameters (TIIP) may lead to improvement in the prediction of phase equilibrium properties such as vapor liquid equilibria, and transport properties e.g., self-diffusivity. Published second virial coefficient data was used to fit a simple two parameter temperature-dependent model for the collision diameter and well depth. This fitting procedure reduces the Root Mean Square Deviation (RMSD) between the experimental and predicted second virial coefficients by tenfold compared to the best TIIP and by 15 fold with the literature values. The vapor–liquid coexistence curve for argon was simulated in the NVT Gibbs ensemble in the temperature range: 110–148 K. The critical temperature and density were determined using the Ising-scaling model. The TDIP simulations produce, in general, a more accurate phase diagram compared to the diagram generated using TIIP. RMSD is reduced by 42.1% using TDIP. Also, there was no significant difference between the results obtained using TDIP and the highly accurate and computationally demanding phase diagrams based on three body contributions implementing Axillrod–Teller correction. Self-diffusivities of atomic argon were evaluated using the mean square displacement or the Einstein method using equilibrium molecular dynamics (MD) at a pressure of 13 bars and a temperature range from 90 K up to 135 K in the isobaric, isothermal NPT ensemble. TDIP, in general, produces more accurate self-diffusivities than the values computed by TIIP simulations. RMSD is reduced by about 64% using the temperature-dependent parameters.

scholarly journals Molecular dynamics simulation studies of lipid bilayer systems.

2000 ◽  
Vol 47 (3) ◽  
pp. 601-611 ◽  
Author(s):  
M Pasenkiewicz-Gierula ◽  
K Murzyn ◽  
T Róg ◽  
C Czaplewski
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Hydrocarbon Chain ◽  
Simulation Method ◽  
Dynamics Simulation ◽  
Single Type ◽  
Membrane Systems ◽  
Structural Element

The main structural element of biological membranes is a liquid-crystalline lipid bilayer. Other constituents, i.e. proteins, sterols and peptides, either intercalate into or loosely attach to the bilayer. We applied a molecular dynamics simulation method to study membrane systems at various levels of compositional complexity. The studies were started from simple lipid bilayers containing a single type phosphatidylcholine (PC) and water molecules (PC bilayers). As a next step, cholesterol (Chol) molecules were introduced to the PC bilayers (PC-Chol bilayers). These studies provided detailed information about the structure and dynamics of the membrane/water interface and the hydrocarbon chain region in bilayers built of various types of PCs and Chol. This enabled studies of membrane systems of higher complexity. They included the investigation of an integral membrane protein in its natural environment of a PC bilayer, and the antibacterial activity of magainin-2. The latter study required the construction of a model bacterial membrane which consisted of two types of phospholipids and counter ions. Whenever published experimental data were available, the results of the simulations were compared with them.

The molecular dynamics simulation on the mechanical properties of Ni glass with external pressure

2017 ◽  
Vol 31 (20) ◽  
pp. 1750138 ◽  
Author(s):  
Chuan-Hui Zhang ◽  
Ying Wang ◽  
Dong-Bai Sun
Keyword(s):  
Molecular Dynamics ◽  
Mean Square Displacement ◽  
External Pressure ◽  
Rapid Quenching ◽  
Distribution Functions ◽  
Dynamics Simulation ◽  
Mean Square ◽  
External Pressures ◽  
Ratio Rule ◽  
Pair Distribution Functions

In this paper, rapid quenching of Ni from crystal to metallic glass (MG) at different external pressures is simulated by molecular dynamics. The pair distribution functions (PDFs), mean-square displacement, glass transition temperature ([Formula: see text]) and elastic property are calculated and compared with each other. The split of the second PDF peak means the liquid’s transition to glass state starts as previously reported for other MGs. And the [Formula: see text] ratio rule is found to hold very well in Ni MG and reveals the SPO structural feature in the configurations. Moreover, with high external pressure, [Formula: see text] values are more approximated by density–temperature and enthalpy–temperature curves. At last, the elastic modulus and mechanics modulus of quenching models produced a monotonous effect with increasing external pressure and temperature.

Reversibly Sampling Conformations and Binding Modes Using Molecular Darting

2020 ◽  
Author(s):  
Samuel C. Gill ◽  
David Mobley
Keyword(s):  
Monte Carlo ◽  
Ligand Binding ◽  
Binding Sites ◽  
Degrees Of Freedom ◽  
Dynamics Simulation ◽  
Hiv Integrase ◽  
Binding Modes ◽  
System A ◽  
Multiple Binding ◽  
Internal Degrees Of Freedom

<div>Sampling multiple binding modes of a ligand in a single molecular dynamics simulation is difficult. A given ligand may have many internal degrees of freedom, along with many different ways it might orient itself a binding site or across several binding sites, all of which might be separated by large energy barriers. We have developed a novel Monte Carlo move called Molecular Darting (MolDarting) to reversibly sample between predefined binding modes of a ligand. Here, we couple this with nonequilibrium candidate Monte Carlo (NCMC) to improve acceptance of moves.</div><div>We apply this technique to a simple dipeptide system, a ligand binding to T4 Lysozyme L99A, and ligand binding to HIV integrase in order to test this new method. We observe significant increases in acceptance compared to uniformly sampling the internal, and rotational/translational degrees of freedom in these systems.</div>

Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes Using Nonequilibrium Candidate Monte Carlo

2017 ◽  
Author(s):  
Samuel Gill ◽  
Nathan M. Lim ◽  
Patrick Grinaway ◽  
Ariën S. Rustenburg ◽  
Josh Fass ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Ligand Binding ◽  
Binding Mode ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Binding Modes ◽  
Enhanced Sampling ◽  
Recent Success ◽  
Multiple Binding ◽  
Proper Sampling

<div>Accurately predicting protein-ligand binding is a major goal in computational chemistry, but even the prediction of ligand binding modes in proteins poses major challenges. Here, we focus on solving the binding mode prediction problem for rigid fragments. That is, we focus on computing the dominant placement, conformation, and orientations of a relatively rigid, fragment-like ligand in a receptor, and the populations of the multiple binding modes which may be relevant. This problem is important in its own right, but is even more timely given the recent success of alchemical free energy calculations. Alchemical calculations are increasingly used to predict binding free energies of ligands to receptors. However, the accuracy of these calculations is dependent on proper sampling of the relevant ligand binding modes. Unfortunately, ligand binding modes may often be uncertain, hard to predict, and/or slow to interconvert on simulation timescales, so proper sampling with current techniques can require prohibitively long simulations. We need new methods which dramatically improve sampling of ligand binding modes. Here, we develop and apply a nonequilibrium candidate Monte Carlo (NCMC) method to improve sampling of ligand binding modes.</div><div><br></div><div>In this technique the ligand is rotated and subsequently allowed to relax in its new position through alchemical perturbation before accepting or rejecting the rotation and relaxation as a nonequilibrium Monte Carlo move. When applied to a T4 lysozyme model binding system, this NCMC method shows over two orders of magnitude improvement in binding mode sampling efficiency compared to a brute force molecular dynamics simulation. This is a first step towards applying this methodology to pharmaceutically relevant binding of fragments and, eventually, drug-like molecules. We are making this approach available via our new Binding Modes of Ligands using Enhanced Sampling (BLUES) package which is freely available on GitHub.</div>

Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes Using Nonequilibrium Candidate Monte Carlo

2018 ◽  
Author(s):  
Samuel Gill ◽  
Nathan M. Lim ◽  
Patrick Grinaway ◽  
Ariën S. Rustenburg ◽  
Josh Fass ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Ligand Binding ◽  
Binding Mode ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Binding Modes ◽  
Enhanced Sampling ◽  
Recent Success ◽  
Multiple Binding ◽  
Proper Sampling

<div>Accurately predicting protein-ligand binding is a major goal in computational chemistry, but even the prediction of ligand binding modes in proteins poses major challenges. Here, we focus on solving the binding mode prediction problem for rigid fragments. That is, we focus on computing the dominant placement, conformation, and orientations of a relatively rigid, fragment-like ligand in a receptor, and the populations of the multiple binding modes which may be relevant. This problem is important in its own right, but is even more timely given the recent success of alchemical free energy calculations. Alchemical calculations are increasingly used to predict binding free energies of ligands to receptors. However, the accuracy of these calculations is dependent on proper sampling of the relevant ligand binding modes. Unfortunately, ligand binding modes may often be uncertain, hard to predict, and/or slow to interconvert on simulation timescales, so proper sampling with current techniques can require prohibitively long simulations. We need new methods which dramatically improve sampling of ligand binding modes. Here, we develop and apply a nonequilibrium candidate Monte Carlo (NCMC) method to improve sampling of ligand binding modes.</div><div><br></div><div>In this technique the ligand is rotated and subsequently allowed to relax in its new position through alchemical perturbation before accepting or rejecting the rotation and relaxation as a nonequilibrium Monte Carlo move. When applied to a T4 lysozyme model binding system, this NCMC method shows over two orders of magnitude improvement in binding mode sampling efficiency compared to a brute force molecular dynamics simulation. This is a first step towards applying this methodology to pharmaceutically relevant binding of fragments and, eventually, drug-like molecules. We are making this approach available via our new Binding Modes of Ligands using Enhanced Sampling (BLUES) package which is freely available on GitHub.</div>

scholarly journals Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 686 ◽  
Author(s):  
Alexander Neumann ◽  
Viktor Engel ◽  
Andhika B. Mahardhika ◽  
Clara T. Schoeder ◽  
Vigneshwaran Namasivayam ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
G Protein ◽  
Phenyl Ring ◽  
Binding Mode ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Binding Modes ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

GPR18 is an orphan G protein-coupled receptor (GPCR) expressed in cells of the immune system. It is activated by the cannabinoid receptor (CB) agonist ∆9-tetrahydrocannabinol (THC). Several further lipids have been proposed to act as GPR18 agonists, but these results still require unambiguous confirmation. In the present study, we constructed a homology model of the human GPR18 based on an ensemble of three GPCR crystal structures to investigate the binding modes of the agonist THC and the recently reported antagonists which feature an imidazothiazinone core to which a (substituted) phenyl ring is connected via a lipophilic linker. Docking and molecular dynamics simulation studies were performed. As a result, a hydrophobic binding pocket is predicted to accommodate the imidazothiazinone core, while the terminal phenyl ring projects towards an aromatic pocket. Hydrophobic interaction of Cys251 with substituents on the phenyl ring could explain the high potency of the most potent derivatives. Molecular dynamics simulation studies suggest that the binding of imidazothiazinone antagonists stabilizes transmembrane regions TM1, TM6 and TM7 of the receptor through a salt bridge between Asp118 and Lys133. The agonist THC is presumed to bind differently to GPR18 than to the distantly related CB receptors. This study provides insights into the binding mode of GPR18 agonists and antagonists which will facilitate future drug design for this promising potential drug target.

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