Search results for " bonding"
showing 10 items of 934 documents
Free-energy studies reveal a possible mechanism for oxidation-dependent inhibition of MGL
2016
AbstractThe function of monoacylglycerol lipase (MGL), a key actor in the hydrolytic deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2AG), is tightly controlled by the cell’s redox state: oxidative signals such as hydrogen peroxide suppress MGL activity in a reversible manner through sulfenylation of the peroxidatic cysteines, C201 and C208. Here, using as a starting point the crystal structures of human MGL (hMGL), we present evidence from molecular dynamics and metadynamics simulations along with high-resolution mass spectrometry studies indicating that sulfenylation of C201 and C208 alters the conformational equilibrium of the membrane-associated lid domain of MGL to favo…
Insights into the inhibited form of the redox-sensitive SufE-like sulfur acceptor CsdE
2017
17 p.-8 fig.
Evaluating the stability of pharmacophore features using molecular dynamics simulations.
2016
Abstract Molecular dynamics simulations of twelve protein—ligand systems were used to derive a single, structure based pharmacophore model for each system. These merged models combine the information from the initial experimental structure and from all snapshots saved during the simulation. We compared the merged pharmacophore models with the corresponding PDB pharmacophore models, i.e., the static models generated from an experimental structure in the usual manner. The frequency of individual features, of feature types and the occurrence of features not present in the static model derived from the experimental structure were analyzed. We observed both pharmacophore features not visible in …
Thiazole–amino acids: influence of thiazole ring on conformational properties of amino acid residues
2021
Abstract Post-translational modified thiazole–amino acid (Xaa–Tzl) residues have been found in macrocyclic peptides (e.g., thiopeptides and cyanobactins), which mostly inhibit protein synthesis in Gram + bacteria. Conformational study of the series of model compounds containing this structural motif with alanine, dehydroalanine, dehydrobutyrine and dehydrophenylalanine were performed using DFT method in various environments. The solid-state crystal structure conformations of thiazole–amino acid residues retrieved from the Cambridge Structural Database were also analysed. The studied structural units tend to adopt the unique semi-extended β2 conformation; which is stabilised mainly by N–H⋯N…
Closed-Locked and Apo-Resting State Structures of the Human α7 Nicotinic Receptor: A Computational Study
2018
International audience; Nicotinic acetylcholine receptors, belonging to the Cys-loop super-family of ligand-gated ion channels (LGICs), are membrane proteins present in neurons and at neuromuscular junctions. They are responsible for signal transmission, and their function is regulated by neurotransmitters, agonists and antagonists drugs. A detailed knowledge of their conformational transition in response to ligand binding is critical to understand the basis of ligand-receptor interaction, in view of new pharmacological approaches to control receptor activity. However, the scarcity of experimentally derived structures of human channels makes this perspective extremely challenging. To contri…
A possible desensitized state conformation of the human α7 nicotinic receptor: A molecular dynamics study
2017
International audience; The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing. The characterization of the desensitized conformation(s) is even more complex, and only few specific characteristics have been identified. Furthermore, exp…
Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo-Switchable Fluorescent Protein
2015
Reversibly switchable fluorescent proteins (RSFPs) are essential for high-resolution microscopy of biological samples, but the reason why these proteins are photochromic is still poorly understood. To address this problem, we performed molecular dynamics simulations of the fast switching Met159Thr mutant of the RSFP Dronpa. Our simulations revealed a ground state structural heterogeneity in the chromophore pocket that consists of three populations with one, two, or three hydrogen bonds to the phenolate moiety of the chromophore. By means of non-adiabatic quantum mechanics/molecular dynamics simulations, we demonstrated that the subpopulation with a single hydrogen bond is responsible for of…
All bonds are not the same: A response surface analysis of the perceptions of positive bonding relationships in therapy groups
2017
Intrapersonal split alliances were defined as discrepancies in how group members perceived their positive bonding relationships with the group leader, the other group members, and the group-as-a-whole, and were related to group members' outcome. Participants were 168 patients (116 women and 52 men) diagnosed as overweight or obese who participated in 1 of 20, 12-session, therapy groups for weight management. Group members completed the Outcome Questionnaire-45 (OQ-45, Lambert et al., 2004) pre- and posttreatment and the Group Questionnaire (GQ, Krogel et al., 2013) at early, middle and late group sessions. Early, middle, and late ratings were aggregated because bond scores were consistent a…
Superfluorinated ionic liquid crystals based on supramolecular, halogen-bonded anions
2016
Unconventional ionic liquid crystals in which the liquid crystallinity is enabled by halogen-bonded supramolecular anions [CnF2 n+1-I⋯I⋯I-CnF2 n+1]- are reported. The material system is unique in many ways, demonstrating for the first time 1) ionic, halogen-bonded liquid crystals, and 2) imidazolium-based ionic liquid crystals in which the occurrence of liquid crystallinity is not driven by the alkyl chains of the cation. Out of the ordinary: The high directionality of halogen bonds and the fluorophobic effect were exploited in the design and synthesis of a new family of unconventional superfluorinated ionic liquid crystals. The liquid crystallinity of the system is driven by halogen-bonded…
Synthesis, characterization, and cytotoxic activity of copper(II) and platinum(II) complexes of 2-benzoylpyrrole and X-ray structure of bis[2-benzoyl…
2004
Copper(II) and platinum(II) complexes of 2-benzoylpyrrole (2-BZPH) were synthesized and characterized with IR, 1 H and 1 3 C NMR spectroscopies and coordination geometry with ligands arranged in transoid fashion. The crystal structure of [Cu I I (2-BZP) 2 ] was determined by X-ray diffraction. Death of complex treated Jurkat cells was measured by flow cytometry. The bis-chelate complexes [Cu I I (2-BZP) 2 ] and [Pt I I (2-BZP) 2 ] adopt square-planar coordination geometry with ligands, arranged in transoid fashion. Concentrations of 1-10 μM Platinum(II) complexes reduced cell survival from 100% to 20%, in contrast to the copper(II) complex which caused no cell death at a concentration of 10…