Search results for "Molecular Dynamic"
showing 10 items of 1090 documents
DNA minor groove binders: an overview on molecular modeling and QSAR approaches
2007
Molecular recognition of DNA by small molecules and proteins is a fundamental problem in structural biology and drug design. Understanding of recognition in both sequence-selective and sequence neutral ways at the level of successful prediction of binding modes and site selectivity will be instrumental for improvements in the design and synthesis of new molecules as potent and selective gene-regulatory drugs. Minor groove is the target of a large number of non-covalent binding agents. DNA binding with specific sequences, mostly AT, takes place by means of a combination of directed hydrogen bonding to base pair edges, van der Waals interactions with the minor groove walls and generalized ele…
Organometallic Oligomers Based on Bis(arylacetylide)bis(P-chirogenic phosphine)platinum(II) Complexes: Synthesis and Photonic Properties
2013
A series of P-chirogenic oligomers of the type (-C≡C-aryl-C≡C-PtL2-)n [L = (R)- and (S)-P(Ph)(iPr)(C17H35); aryl = 1,4-benzene, 2,1,3-benzothiadiazole] along the corresponding achiral analogues (L = PBu3) and model complexes PhC≡CPtL2C≡CPh were prepared from the ephedrine strategy and were fully characterized [(1)H, (31)P NMR; IR; small-angle X-ray scattering (SAXS); gel permeation chromatography (GPC); thermal gravimetric analysis (TGA); circular dichroism, UV-vis, and luminescence spectroscopy; photophysics, and degree of anisotropy measurements]. From the CD measurements, the chiral environment of the phosphine ligands is modestly felt by the aryl moieties. Concurrently, the TGA shows th…
Evidence for substrate binding-induced zwitterion formation in the catalytic Cys-His dyad of the SARS-CoV main protease.
2014
The coronavirus main protease (M(pro)) represents an attractive drug target for antiviral therapy of coronavirus (CoV) infections, including severe acute respiratory syndrome (SARS). The SARS-CoV M(pro) and related CoV proteases have several distinct features, such as an uncharged Cys-His catalytic dyad embedded in a chymotrypsin-like protease fold, that clearly separate these enzymes from archetypical cysteine proteases. To further characterize the catalytic system of CoV main proteases and to obtain information about improved inhibitors, we performed comprehensive simulations of the proton-transfer reactions in the SARS-CoV M(pro) active site that lead to the Cys(-)/His(+) zwitterionic st…
Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.
2012
Ankyrin repeat proteins are elastic materials that unfold and refold sequentially, repeat by repeat, under force. Herein we use atomistic molecular dynamics to compare the mechanical properties of the 7-ankyrin-repeat oncoprotein Gankyrin in isolation and in complex with its binding partner S6-C. We show that the bound S6-C greatly increases the resistance of Gankyrin to mechanical stress. The effect is specific to those repeats of Gankyrin directly in contact with S6-C, and the mechanical ‘hot spots’ of the interaction map to the same repeats as the thermodynamic hot spots. A consequence of stepwise nature of unfolding and the localized nature of ligand binding is that it impacts on all as…
Homology models of melatonin receptors: challenges and recent advances
2013
Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs), named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore …
Combined use of 13C chemical shift and 1H alpha-13C alpha heteronuclear NOE data in monitoring a protein NMR structure refinement.
1995
A large portion of the 13C resonance assignments for murine epidermal growth factor (mEGF) at pH 3.1 and 28 degrees C has been determined at natural isotope abundance. Sequence-specific 13C assignments are reported for 100% of the assignable C alpha, 96% of the C beta, 86% of the aromatic and 70% of the remaining peripheral aliphatic resonances of mEGF. A good correlation was observed between experimental and back-calculated C alpha chemical shifts for regions of regular beta-sheet structure. These assignments also provide the basis for interpreting 1H alpha-13C alpha heteronuclear NOE (HNOE) values in mEGF at natural isotope abundance. Some of the backbone polypeptide segments with high in…
A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model
2014
Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eight non-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledge is scarce on the impact of this and other mutations upon the chaperone's structure and functions. To make progress, experimental models must be developed. We used an archaeal mutant homolog and demonstrated that the His147Arg mutant has impaired oligomeric assembly, ATPase activity, and defective protein homeostasis functions. These results establish for the first time that a human chaperonin gene defect can be reproduced and studied at the molecular level with an archaeal homolog. The major…
The amorphous silica-liquid water interface studied by ab initio molecular dynamics (AIMD): local organization in global disorder
2014
International audience; The structural organization of water at a model of amorphous silica-liquid water interface is investigated by ab initio molecular dynamics (AIMD) simulations at room temperature. The amorphous surface is constructed with isolated, H-bonded vicinal and geminal silanols. In the absence of water, the silanols have orientations that depend on the local surface topology (i.e. presence of concave and convex zones). However, in the presence of liquid water, only the strong inter-silanol H-bonds are maintained, whereas the weaker ones are replaced by H-bonds formed with interfacial water molecules. All silanols are found to act as H- bond donors to water. The vicinal silanol…
A3 adenosine receptor: Homology modeling and 3D-QSAR studies
2012
Adenosine receptors (AR) belong to the superfamily of G-protein-coupled receptors (GPCRs). They are divided into four subtypes (A1, A2A, A2B, and A3) [1], and can be distinguished on the basis of their distinct molecular structures, distinct tissues distribution, and selectivity for adenosine analogs [2,3]. The hA3R, the most recently identified adenosine receptor, is involved in a variety of intracellular signaling pathways and physiological functions [4]. Expression of A3R was reported to be elevated in cancerous tissues [5], and A3 antagonists have been proposed for therapeutic treatments of cancer. The recent literature availability of crystal structure of hA2A adenosine receptor (PDB c…
Molecular dynamics simulation of carboxy-myoglobin embedded in a trehalose-water matrix
2001
AbstractWe report on a molecular dynamics (MD) simulation of carboxy-myoglobin (MbCO) embedded in a water-trehalose system. The mean square fluctuations of protein atoms, calculated at different temperatures in the 100–300K range, are compared with those from a previous MD simulation on an H2O-solvated MbCO and with experimental data from Mössbauer spectroscopy and incoherent elastic neutron scattering on trehalose-coated MbCO. The results show that, for almost all the atomic classes, the amplitude of the nonharmonic motions stemming from the interconversion among the protein’s conformational substates is reduced with respect to the H2O-solvated system, and their onset is shifted toward hig…