Search results for "Molecular Dynamic"
showing 10 items of 1090 documents
The catalytic mechanism of glyceraldehyde 3-phosphate dehydrogenase from Trypanosoma cruzi elucidated via the QM/MM approach
2013
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as a key enzyme involved in glycolysis processes for energy production in the Trypanosoma cruzi parasite. This enzyme catalyses the oxidative phosphorylation of glyceraldehyde 3-phosphate (G3P) in the presence of inorganic phosphate (Pi) and nicotinamide adenosine dinucleotide (NAD+). The catalytic mechanism used by GAPDH has been intensively investigated. However, the individual roles of Pi and the C3 phosphate of G3P (Ps) sites, as well as some residues such as His194 in the catalytic mechanism, remain unclear. In this study, we have employed Molecular Dynamics (MD) simulations within hybrid quantum mechanical/molecular …
Preorganization and reorganization as related factors in enzyme catalysis: the chorismate mutase case.
2003
In this paper a deeper insight into the chorismate-to prephenate-rearrangement, catalyzed by Bacillus subtilis chorismate mutase, is provided by means of a combination of statistical quantum mechanics/molecular mechanics simulation methods and hybrid potential energy surface exploration techniques. The main aim of this work is to present an estimation of the preorganization and reorganization terms of the enzyme catalytic rate enhancement. To analyze the first of these, we have studied different conformational equilibria of chorismate in aqueous solution and in the enzyme active site. Our conclusion is that chorismate mutase preferentially binds the reactive conformer of the substrate--that…
Seeking the Source of Catalytic Efficiency of Lindane Dehydrochlorinase, LinA.
2020
Herein we present the results of an in-depth simulation study of LinA and its two variants. In our analysis, we combined the exploration of protein conformational dynamics with and without bound substrates (hexachlorocyclohexane (HCH) isomers) performed using molecular dynamics simulation followed by the extraction of the most frequently visited conformations and their characteristics with a detailed description of the interactions taking place in the active site between the respective HCH molecule and the first shell residues by using symmetry-adapted perturbation theory (SAPT) calculations. A detailed investigation of the conformational space of LinA substates has been accompanied by desc…
Local vs global motions in protein folding
2013
It is of interest to know whether local fluctuations in a polypeptide chain play any role in the mechanism by which the chain folds to the native structure of a protein. This question is addressed by analyzing folding and non-folding trajectories of a protein; as an example, the analysis is applied to the 37-residue triple β-strand WW domain from the Formin binding protein 28 (FBP28) (PDB ID: 1E0L). Molecular dynamics (MD) trajectories were generated with the coarse-grained united-residue force field, and one- and two-dimensional free-energy landscapes (FELs) along the backbone virtual-bond angle θ and backbone virtual-bond-dihedral angle γ of each residue, and principal components, respect…
Photoinduced DNA Lesions in Dormant Bacteria. The Peculiar Route Leading to Spore Photoproduct Unraveled by Multiscale Molecular Dynamics
2020
Some bacterial species enter a dormant state in the form of spores to resist to unfavorable external conditions. Spores are resistant to a wide series of stress agents, including UV radiation, and can last for tens to hundreds of years. Due to the suspension of biological functions such as DNA repair, they accumulate DNA damage upon exposure to UV radiation. Differently from active organisms, the most common DNA photoproduct in spores are not cyclobutane pyrimidine dimers, but rather the so-called spore photoproduct. This non-canonical photochemistry results from the dry state of DNA and the binding to small acid soluble proteins that drastically modify the structure and photoreactivity of …
Theoretical studies of HIV-1 reverse transcriptase inhibition
2012
Computational methods for accurately calculating the binding affinity of a ligand for a protein play a pivotal role in rational drug design. We herein present a theoretical study of the binding of five different ligands to one of the proteins responsible for the human immunodeficiency virus type 1 (HIV-1) cycle replication; the HIV-1 reverse transcriptase (RT). Two types of approaches are used based on molecular dynamics (MD) simulations within hybrid QM/MM potentials: the alchemical free energy perturbation method, FEP, and the pathway method, in which the ligand is physically pulled away from the binding site, thus rendering a potential of mean force (PMF) for the binding process. Our com…
Conformational dynamics of full-length inducible human Hsp70 derived from microsecond molecular dynamics simulations in explicit solvent
2013
Human 70 kDa heat shock protein (hHsp70) is an ATP-dependent chaperone and is currently an important target for developing new drugs in cancer therapy. Knowledge of the conformations of hHsp70 is central to understand the interactions between its nucleotide-binding domain (NBD) and substrate-binding domain (SBD) and is a prerequisite to design inhibitors. The conformations of ADP-bound (or nucleotide-free) hHsp70 and ATP-bound hHsp70 was investigated by using unbiased all-atom molecular dynamics (MD) simulations of homology models of hHsp70 in explicit solvent on a timescale of .5 and 2.7 μs, respectively. The conformational heterogeneity of hHsp70 was analyzed by computing effective free-e…
Comprehensive Strategy for Proton Chemical Shift Prediction: Linear Prediction with Nonlinear Corrections
2014
A fast 3D/4D structure-sensitive procedure was developed and assessed for the chemical shift prediction of protons bonded to sp3carbons, which poses the maybe greatest challenge in the NMR spectral parameter prediction. The LPNC (Linear Prediction with Nonlinear Corrections) approach combines three well-established multivariate methods viz. the principal component regression (PCR), the random forest (RF) algorithm, and the k nearest neighbors (kNN) method. The role of RF is to find nonlinear corrections for the PCR predicted shifts, while kNN is used to take full advantage of similar chemical environments. Two basic molecular models were also compared and discussed: in the MC model the desc…
A comparative molecular dynamics-phase-field modeling approach to brittle fracture
2016
Abstract In this work, a novel comparative method for highly brittle materials such as aragonite crystals is proposed, which provides an efficient and accurate in-sight understanding for multi-scale fracture modeling. In particular, physically-motivated molecular dynamics (MD) simulations are performed to model quasi-static brittle crack propagation on the nano-scale and followingly compared to macroscopic modeling of fracture using the phase-field modeling (PFM) technique. A link between the two modeling schemes is later proposed by deriving PFM parameters from the MD atomistic simulations. Thus, in this combined approach, MD simulations provide a more realistic meaning and physical estima…
Dynamic Stabilization of the Ligand-Metal Interface in Atomically Precise Gold Nanoclusters Au68 and Au144 Protected by meta-Mercaptobenzoic Acid
2017
Ligand-stabilized, atomically precise gold nanoclusters with a metal core of a uniform size of just 1–3 nm constitute an interesting class of nanomaterials with versatile possibilities for applications due to their size-dependent properties and modifiable ligand layers. The key to extending the usability of the clusters in applications is to understand the chemical bonding in the ligand layer as a function of cluster size and ligand structure. Previously, it has been shown that monodispersed gold nanoclusters, stabilized by meta-mercaptobenzoic acid (m-MBA or 3-MBA) ligands and with sizes of 68–144 gold atoms, show ambient stability. Here we show that a combination of nuclear magnetic reson…