Search results for "molecular dynamics"
showing 10 items of 1075 documents
Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection
2021
The identification of chemical compounds able to bind specific sites of the human/viral proteins involved in the SARS-CoV-2 infection cycle is a prerequisite to design effective antiviral drugs. Here we conduct a molecular dynamics study with the aim to assess the interactions of ivermectin, an antiparasitic drug with broad-spectrum antiviral activity, with the human Angiotensin-Converting Enzyme 2 (ACE2), the viral 3CLpro and PLpro proteases, and the viral SARS Unique Domain (SUD). The drug/target interactions have been characterized in silico by describing the nature of the non-covalent interactions found and by measuring the extent of their time duration along the MD simulation. Results …
Frontiers of metal-coordinating drug design
2020
INTRODUCTION: The occurrence of metal ions in biomolecules is required to exert vital cellular functions. Metal-containing biomolecules can be modulated by small-molecule inhibitors targeting their metal-moiety. As well, the discovery of cisplatin ushered the rational discovery of metal-containing-drugs. The use of both drug types exploiting metal–ligand interactions is well established to treat distinct pathologies. Therefore, characterizing and leveraging metal-coordinating drugs is a pivotal, yet challenging, part of medicinal chemistry. AREA COVERED: Atomic-level simulations are increasingly employed to overcome the challenges met by traditional drug-discovery approaches and to compleme…
Toward a Rationale for the PTC124 (Ataluren) Promoted Readthrough of Premature Stop Codons: A Computational Approach and GFP-Reporter Cell-Based Assay
2014
The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination c…
A distributed dynamic load balancer and its implementation on multi-transputer systems for molecular dynamics simulation
1990
Abstract A new and efficient approach is described to the dynamic load-balancing problem which is central in concurrent computing. A transputer-based implementation is tested on a molecular dynamics simulation of spinodal phase separation.
Comparative Study of the Mechanical Unfolding Pathways of α- and β-Peptides
2015
Using molecular simulations, we analyze the unfolding pathways of various peptides. We compare the mechanical unfolding of a β-alanine's octamer (β-HAla8) and an α-alanine's decamer (α-Ala10). Using force-probe molecular-dynamics simulations, to induce unfolding, we show that the 3(14)-helix formed by β-HAla8 is mechanically more stable than the α-helix formed by α-Ala10, although both structures are stabilized by six hydrogen bonds. Additionally, computations of the potential of mean force validate this result and show that also the thermal stability of the 3(14)-helix is higher. It is demonstrated that β-HAla8 unfolds in a two-step fashion with a stable intermediate. This is contrasted wi…
Solid-state diffusion phenomena in heterogeneous gas-solid reactions : Application to oxides sulfidation
2018
Phase transition phenomena involving the mobility of the reaction interface are involved in a wide variety of chemical reactions and applications. A good example is the sulfidation reaction experienced by the metal oxide-based materials used in the framework of gas purification or catalysts preparation applications. These reactions involve solid-state diffusion phenomena of the reactive species (atomic or ionic form) through the layer of product formed during the reaction (oxide, sulfide, or metal phase). In many cases, solid-state diffusion has a direct impact on the reaction mechanisms while determining the growth direction of the formed phases, as well as the overall kinetics of the reac…
Hybrid QM/MM Molecular Dynamics with AMOEBA Polarizable Embedding
2017
International audience; We present the implementation of a Born-Oppenheimer (BO) hybrid Quantum Mechan-ics/Molecular Mechanics (QM/MM) Molecular Dynamics (MD) strategy using Density Functional Theory (DFT) and the polarizable AMOEBA force field. This approach couples the Gaussian and Tinker suite of programs through a variational formalism allowing for a full self-consistent relaxation of both the AMOEBA induced dipoles and the DFT electronic density at each MD step. As the DFT SCF cycles are the limiting factor in terms of computational efforts and MD stability, we focus on the latter aspect and compare the Time-Reversible BO (TR– BO) and the Extended BO Lagrangian approaches (XL–BO) to th…
A small spherical liquid: A DFT molecular dynamics study of WAu12
2009
The finite-temperature dynamics of WAu12, incorporating both electronic and structural effects, is studied using a density-functional-based Born-Oppenheimer molecular dynamics method. Molecular dynamics simulations for monomolecular WAu12 suggest a surface-melting-type behaviour of the angular degrees of freedom between 366 and 512 K. Thermally averaged electron density-of-states of WAu12 are compared to the experimental photoelectron spectra of WAu12(-).
Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations
2018
Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both impli…
Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1-42) peptides and dimeric splitting phenomena.
2022
International audience; The Aβ(1-42) aggregation is a key event in the physiopathology of Alzheimer's disease (AD). Exogenous factors such as environmental pollutants, and more particularly pesticides, can corrupt Aβ(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of Aβ(1-42) aggregation is still unknown. Here, we employed conical track-etched nanopore in order to analyse the Aβ(1-42) fibril formation in the presence of pyrimethanil, a widely used fungicide belonging to the anilinopyrimidine class. Our results evidenced a pro-aggregating effect of pyrimethanil on Aβ(1-42). Aβ(1-42) assemblies were successfully d…