A5016563552- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Spectroscopy and Quantum Chemical Studies
- Computational Drug Discovery Methods
- Neuroendocrine regulation and behavior
- Free Radicals and Antioxidants
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Surfactants and Colloidal Systems
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Redox biology and oxidative stress
- DNA Repair Mechanisms
- Antimicrobial Peptides and Activities
- Phase Equilibria and Thermodynamics
- Advanced Chemical Physics Studies
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Molecular Spectroscopy and Structure
- Neurobiology and Insect Physiology Research
- nanoparticles nucleation surface interactions
- Electron Spin Resonance Studies
- Sulfur Compounds in Biology
University of Szeged
2012-2022
Aarhus University
2011
Gedeon Richter (Hungary)
2008
Weatherford College
2007
University of Toronto
2006
Abstract The aim of this work was to answer the question whether general amber force field (GAFF) is good enough simulate fully hydrated POPC membrane bilayers. test system contained 128 and 2985 TIP3P water molecules. equilibration carried out in a nonarbitrary manner reach stable liquid‐crystalline phase. simulations were performed by using particle mesh Ewald electrostatics implemented molecular dynamics packages Amber8 (NPT ensembles) NAMD2 (NPγT ensembles). computational results...
The formation of ligand-protein complexes requires simultaneous adaptation the binding partners. In structure based virtual screening, high throughput docking approaches typically consider ligand flexibility, but conformational freedom protein is usually taken into account in a limited way. goal this study to elaborate methodology for incorporating flexibility improve screening enrichments on GPCRs. Explicit-solvated molecular dynamics simulations (MD) were carried out lipid bilayers...
Micellisation process for sodium dodecyl sulphate and cholate in 1∶1 molar ratio was investigated a combined approach, including several experimental methods coarse grained molecular dynamics simulation. The critical micelle concentration (cmc) of mixed determined by spectrofluorimetric surface tension measurements the temperature range 0–50°C values obtained agreed with each other within statistical error measurements. In 0–25°C cmc are independent while were increased at higher...
Non-reactive, comparative (2 × 1.2 μs) molecular dynamics simulations were carried out to characterize the interactions between glutathione (GSH, host molecule) and hydroxyl radical (OH(•), guest molecule). From this analysis, two distinct steps identified in recognition process of by glutathione: catching steering, based on host-guest molecules. Over 78% all are related mechanism via complex formation anionic carboxyl groups OH radical, hence both terminal residues GSH serve as sites. The...
Penicillin, travels through bodily fluids, targeting and acylatively inactivating enzymes responsible for cell-wall synthesis in gram-positive bacteria. Somehow, it avoids metabolic degradation remaining inactive en route. To resolve this ability to switch from a non-active, highly reactive form, we investigated the dynamic structure-activity relationship of penicillin by inelastic neutron spectroscopy, reaction kinetics, NMR multi-scale theoretical modelling (QM/MM post-HF ab initio)....
All possible X-H (where X can be C, N, O or S) bond dissociation energies (BDEs) of glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH) and its fragments have been calculated by first principle methods, the antioxidant potential GSH was revealed to higher than expected in earlier studies. Electron delocalization found an important influence on potential. structures were optimized their harmonic vibrational frequencies gas phase at B3LYP/6-31G(d) level theory. Solvent effects taken into...
Molecular dynamics simulations of the liquid–vapor interface acetone–water mixtures different compositions, covering entire composition range have been performed on canonical (N, V, T) ensemble at 298 K, using a model combination that excellently describes mixing properties these compounds. The intrinsic liquid surfaces analyzed in terms Identification Truly Interfacial Molecules (ITIM) method. Thus, composition, width, roughness, and separation subsurface molecular layers, as well...
It has always been a question of considerable scientific interest why amino acids (and other biomolecule building blocks) formed and accumulated in the prebiotic ocean. In this study, we suggest an answer to for simplest acid, glycine. We have shown first time that classical equilibrium thermodynamics can explain most likely selection glycine derivative its dipeptide) aqueous media, although is not lowest free energy structure among all (404) possible constitutional isomers. Species...
EDTA is commonly used as an efficient chelator of metal ion enzyme cofactors. It highly soluble, optically inactive and does not interfere with most chemicals in standard buffers making a common choice to generate metal-free conditions for biochemical biophysical investigations. However, the controversy literature on activities achieved using or by other means called our attention putative effect beyond chelation. Here, we show that competes nucleotide binding site hydrolase dUTPase...
The energetics of peptide bond formation is an important factor not only in the design chemical synthesis, but it also has a role protein biosynthesis. In this work, quantum calculations at 10 different levels theory including G3MP2B3 were performed on glutathione formation. strength found to be closely related acid to-be N-terminal and basicity C-terminal amino acid. It shown that first activates for next condensation step, manifested bacterial synthesis where step N-formylmethionine...
Molecular dynamics simulations of the liquid–vapour interface acetone have been performed in canonical (N, V, T) ensemble at 298 K with two different molecular models, belonging to transferable potential for phase equilibria (TraPPE) and Chemistry Harvard Mechanics 27 (CHARMM27) force fields, respectively. The first three layers liquid beneath its surface identified by means identification truly interfacial molecules (ITIM) method. results obtained reveal that vicinity vapour affects only...
The recently solved crystal structure of the human adenosine A2A receptor (hA2AR) shows characteristics a partially activated state. Experimental data suggests that high sodium chloride concentration shifts hA2AR to inactive We found molecular dynamics simulations at result in an form reflected reformation "ionic lock" (Arg102(3.50)−Glu228(6.30)) as well reduction αC−αC distance between intracellular sides transmembrane helices 3 and 6 (TM3 TM6). Interestingly, no such stabilization effect...
1,4-Dioxane is a cytotoxic B2-type human carcinogen, serious water pollutant produced solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed dipalmitoyl-phosphatidylcholine (DPPC) and its branched isomer (isodipalmitoyl-phosphatidylcholine, IPPC) was investigated using MD simulations. Clear polluted membranes were compared parameters such as area per lipid (APL), volume (VPL), compressibility modulus, thickness, orderliness tails. While neat systems...
In spite of recent investigations into the potential pharmaceutical importance bile acids as drug carriers, structure acid aggregates is largely unknown. Here, we used global optimization techniques to find lowest energy configurations for clusters composed between 2 and 10 cholate molecules, evaluated relative stabilities minima. We found that energetically most preferred geometries small are in fact reverse micellar arrangements, classical behaviour (efficient burial hydrophobic parts)...
Abstract We report the identification of novel histamine H4 receptor ligands by ensemble docking on homology model conformers derived from molecular dynamics simulations. Selected models trajectories demonstrated superior virtual screening performance compared to initial models. The best was able retrieve a diverse set known ligands. Prospective against these and subsequent in vitro experimental validation identified Compound 3 showing highest affinity ligand efficiency represents an...
The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold antimicrobial peptide PGLa, we have developed foldamers with a computer-guided design strategy. novel PGLa analogues induce sustained hyperpolarization. When co-administered as an adjuvant, resulting compounds - PGLb1 and PGLb2 substantially reduced level antibiotic resistance multi-drug resistant Escherichia coli, Klebsiella pneumoniae Shigella flexneri clinical...
Metabotropic glutamate receptor 5 (mGluR5) is a class C G protein-coupled (GPCR) with both an extracellular ligand binding site and allosteric intrahelical chamber located similarly to the orthosteric of Class A GPCRs. Ligands this ancestral mGluR5 can act as positive (PAM), negative (NAM) or silent (SAM) modulators, their medicinal chemistry optimization notoriously difficult, subtle structural changes may cause significant variation in activity switch functional response. Here we present...