Search results for "MOLECULAR MODELING"
showing 10 items of 136 documents
Phosphinotripeptidic Inhibitors of Leucylaminopeptidases
2021
Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of phosphinate pseudopeptides make them an ideal candidate for metal-related protease inhibitors. This research investigates the influence of additional residue in the P2 position on the inhibitory properties of phosphinopeptides. The synthetic strategy is proposed, based on retrosynthetic analysis. The N-C-P bond formation in the desired compounds is …
Molecular basis of SARS-CoV-2 infection and rational design of potential antiviral agents: Modeling and simulation approaches
2020
International audience; The emergence in late 2019 of the coronavirus SARS-CoV-2 has resulted in the breakthrough of the COVID-19 pandemic that is presently affecting a growing number of countries. The development of the pandemic has also prompted an unprecedented effort of the scientific community to understand the molecular bases of the virus infection and to propose rational drug design strategies able to alleviate the serious COVID-19 morbidity. In this context, a strong synergy between the structural biophysics and molecular modeling and simulation communities has emerged, resolving at the atomistic level the crucial protein apparatus of the virus and revealing the dynamic aspects of k…
Assessing Human Genetic Variations in Glucose Transporter SLC2A10 and Their Role in Altering Structural and Functional Properties
2018
Purpose: Demand is increasing for clinical genomic sequencing to provide diagnoses for patients presenting phenotypes indicative of genetic diseases, but for whom routine genetic testing failed to yield a diagnosis. DNA-based testing using high-throughput technologies often identifies variants with insufficient evidence to determine whether they are disease-causal or benign, leading to categorization as variants of uncertain significance (VUS). Methods: We used molecular modeling and simulation to generate specific hypotheses for the molecular effects of variants in the human glucose transporter, GLUT10 (SLC2A10). Similar to many disease-relevant membrane proteins, no experimentally derived…
Sensitivity of 3He NMR parameters to the proximity of heterocyclic rings. The helium–furan dimer
2014
The potential of NMR technique in probing the interaction between a noble gas atom (used as a spectroscopic probe) and five-membered heterocyclic systems was theoretically studied. Selected 3He NMR parameters of free noble gas atom and its dimer were calculated using density functional theory with three functionals (M06-2X, CAM-B3LYP, and APFD), combined with dedicated polarization-consistent basis sets, and critically compared with theoretical high level calculations from the literature. The change of sotropic nuclear magnetic shielding of free noble gas atom in the presence of furan (3He placed above he middle of the ring and used as NMR probe) increased with its proximity to the heterocy…
Error estimation and reduction with cross correlations
2010
Besides the well-known effect of autocorrelations in time series of Monte Carlo simulation data resulting from the underlying Markov process, using the same data pool for computing various estimates entails additional cross correlations. This effect, if not properly taken into account, leads to systematically wrong error estimates for combined quantities. Using a straightforward recipe of data analysis employing the jackknife or similar resampling techniques, such problems can be avoided. In addition, a covariance analysis allows for the formulation of optimal estimators with often significantly reduced variance as compared to more conventional averages.
A highly enantioselective abiotic receptor for malate dianion in aqueous solution
2006
The highly enantioselective molecular recognition of the malate dianion by a synthetic receptor in aqueous solution has been studied by potentiometric titrations, mass spectrometry (ESI-MS), diffusion measurements (PGSE NMR) and molecular modeling. Garcia-España Monsonis, Enrique, Enrique.Garcia-Es@uv.es
Polycerasoidol, a Natural Prenylated Benzopyran with a Dual PPARα/PPARγ Agonist Activity and Anti-inflammatory Effect
2019
Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed th…
A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies
2019
In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the …
Sensitivity of noble gas NMR parameters to the heterocyclic ring proximity. Density functional theory studies of Ne–furan and Ar–furan complexes
2014
Theoretical modeling of noble gas interaction with furan as a simple heterocyclic ring was performed. The structures of neon–furan and argon–furan complexes were calculated at the MP2, M06-2X, CAM-B3LYP, APFD, and VSXC levels of theory using 6-311++G** basis set. The predicted 21Ne and 39Ar NMR chemical shifts for the Ne–furan and Ar–furan complexes calculated with pcS-3 and aug-pcS-3 basis sets were sensitive to the presence of the aromatic furan ring. Our results indicate a higher sensitivity of the neon and argon NMR probes than the previously reported 3He NMR spectroscopic parameters in studies of small heterocyclic rings containing the oxygen atom.
How far the substituent effects in disubstituted cyclohexa-1,3-diene derivatives differ from those in bicyclo[2.2.2]octane and benzene?
2018
Substituents effects in cyclic diene derivatives are studied using quantum chemical modeling and compared to the corresponding effects in aromatic (benzene) and fully saturated (bicyclo[2.2.2]octane) compounds. In particular, electronic properties of the fixed group Y in a series of 3- and 4-X-substituted cyclohexa-1,3-diene-Y derivatives (where Y = NO2, COOH, COO− OH, O−, NH2, and X = NMe2, NH2, OH, OMe, Me, H, F, Cl, CF3, CN, CHO, COMe, CONH2, COOH, NO2, NO) are examined using the B3LYP/6-311++G(d,p) method. For this purpose, quantum chemistry models of the substituent effect: cSAR (charge of the substituent active region) and SESE (substituent effect stabilization energy) as well as trad…