A5010899423- Computational Drug Discovery Methods
- Cystic Fibrosis Research Advances
- Machine Learning in Materials Science
- Protein Structure and Dynamics
- Advanced biosensing and bioanalysis techniques
- Advanced Chemical Physics Studies
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Plant-Microbe Interactions and Immunity
- Adenosine and Purinergic Signaling
- Spectroscopy and Quantum Chemical Studies
- Plant Pathogenic Bacteria Studies
- Carbohydrate Chemistry and Synthesis
- Fluorine in Organic Chemistry
- Neonatal Respiratory Health Research
- Genomics, phytochemicals, and oxidative stress
- Molecular Spectroscopy and Structure
- DNA and Nucleic Acid Chemistry
- Analytical Chemistry and Chromatography
- Bacterial biofilms and quorum sensing
- Lanthanide and Transition Metal Complexes
- Monoclonal and Polyclonal Antibodies Research
- Legume Nitrogen Fixing Symbiosis
- Peptidase Inhibition and Analysis
Bar-Ilan University
2016-2025
Alzheimer's Association of Israel
2018
Hebrew University of Jerusalem
2007-2014
University of Münster
2014
University Hospital Frankfurt
2014
Goethe University Frankfurt
2014
Temple University
2014
Centre National de la Recherche Scientifique
2011
Université d'Orléans
2011
Université de Strasbourg
2011
The deletion of phenylalanine 508 in the first nucleotide binding domain cystic fibrosis transmembrane conductance regulator is directly associated with >90% cases. This mutant protein fails to traffic out endoplasmic reticulum and subsequently degraded by proteasome. effects this mutation may be partially reversed application exogenous osmolytes, expression at low temperature, introduction second site suppressor mutations. However, specific steps folding assembly full-length (CFTR) altered...
DNA is an important target for the treatment of multiple pathologies, most notably cancer. In particular, intercalators have often been used as anticancer drugs. However, despite their relevance to drug discovery, only a few systematic computational studies were performed on DNA-intercalator complexes. this work we analyzed ligand binding sites preferences in 63 high resolution complexes available PDB and found that ligands bind preferentially between G C A base pairs (70% 11%,...
Carbohydrates are thought to be especially difficult model because of their highly polar functionality, flexibility, and differences in electronic arrangements that occur during conformational configurational changes, such as the anomeric, exo-anomeric gauche effects. These issues have been addressed recent years, yielding several contributions set up some relevant parameterizations would account for these specific features carbohydrates. Within framework a workshop involving participation...
Adenosine 5'-monophosphate activated protein kinase (AMPK) has emerged as a major potential target for novel antidiabetic drugs. We studied the structure of 2-chloro-5-((Z)-((E)-5-((5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl)methylene)-4-oxothiazolidin-2-ylidene)amino)benzoic acid (PT-1), which attenuates autoinhibition enzyme AMPK, design and synthesis different benzothiazoles with activity. synthesized several structurally related benzothiazole derivatives that increased rate glucose uptake...
Quorum sensing (QS) is a population density-dependent regulatory system in bacteria that couples gene expression to cell density through accumulation of diffusible signaling molecules. Pectobacteria are causal agents soft rot disease range economically important crops. They rely on QS coordinate their main virulence factor, production plant wall degrading enzymes (PCWDEs). Plants have evolved an array antimicrobial compounds anticipate and cope with pathogens, which essential oils (EOs)...
Abstract QSAR models are widely and successfully used in many research areas. The success of such highly depends on molecular descriptors typically classified as 1D, 2D, 3D, or 4D. While 3D information is likely important, e. g., for modeling ligand‐protein binding, previous comparisons between the performances 2D were inconclusive. Yet modeled ligands not necessarily represented by their bioactive conformations. With this mind, we mined PDB sets protein‐ligand complexes sharing same protein...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Smart Monte Carlo Technique for Free Energy Simulations of Multiconformational Molecules. Direct Calculations the Conformational Populations Organic MoleculesHanoch Senderowitz, Frank Guarnieri, and W. Clark StillCite this: J. Am. Chem. Soc. 1995, 117, 31, 8211–8219Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August...
The success of molecular modeling using classical potential functions (i.e force field calculations) rests heavily on the availability specific, high-quality parameters that accurately describe gas phase surface system under study, solvent models reliably reproduce effect medium, and simulation methods sample all significantly populated conformations entire with correct statistical weights. In this paper we present a set mechanics were developed ab initio orbital calculations to model...
Deletion of Phe-508 (F508del) in the first nucleotide binding domain (NBD1) cystic fibrosis transmembrane conductance regulator (CFTR) leads to defects folding and channel gating. NMR data on human F508del NBD1 indicate that an H620Q mutant, shown increase open probability, dual corrector/potentiator CFFT-001 similarly disrupt interactions between β-strands S3, S9, S10 C-terminal helices H8 H9, shifting a preexisting conformational equilibrium from helix coil. appears interact with...
ABSTRACT To enhance the efficacy of targeted drug delivery, four new peptide‐ligand conjugates were synthesized, each consisting a cyclic RGDfK penta‐peptide loaded with two anticancer drugs. The release profiles in different media these compounds and their cytotoxic activity against melanoma non‐small lung cancer cell lines evaluated compared those singly analogs. was selected as targeting moiety because its high affinity selectivity to α v β 3 integrin receptor, which is frequently...
Abstract Growth in energy demands, coupled with the need for clean energy, are likely to make solar cells an important part of future resources. In particular, entirely made metal oxides (MOs) have potential provide and affordable if their power conversion efficiencies improved. Such improvements require development new MOs which could benefit from combining combinatorial material sciences producing libraries data mining tools direct synthesis efforts. this work we developed a workflow...
Aberrant nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is associated with chondrocalcinosis, osteoarthritis, and type 2 diabetes. The potential of NPP1 inhibitors as therapeutic agents, the scarceness their structure-activity relationship, encouraged us to develop new inhibitors. Specifically, we synthesized ATP-α-thio-β,γ-CH2 (1), ATP-α-thio-β,γ-CCl2 (2), ATP-α-CH2-γ-thio (3), 8-SH-ATP (4) established resistance hydrolysis by NPP1,3 NTPDase1,2,3,8 (<5% hydrolysis) (NTPDase...
Adult polyglucosan body disease (APBD) is a late-onset caused by intracellular accumulation of bodies, formed due to glycogen-branching enzyme (GBE) deficiency. To find treatment for APBD, we screened 1,700 FDA-approved compounds in fibroblasts derived from APBD-modeling GBE1-knockin mice. Capitalizing on fluorescent periodic acid-Schiff reagent, which interacts with polyglucosans the cell, this screen discovered that flavoring agent guaiacol can lower polyglucosans, result also confirmed...
Patients with cystic fibrosis (CF) harboring the P67L variant in transmembrane conductance regulator (CFTR) often exhibit a typical CF phenotype, including severe respiratory compromise. This rare mutation (reported <300 patients worldwide) responds robustly to CFTR correctors, such as lumacaftor and tezacaftor, rescue model systems that far exceed what can be achieved for archetypical mutant F508del. However, specific molecular consequences of are poorly characterized. In this study, we...
Elevated nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is implicated in health disorders including pathological calcification. Specific NPP1 inhibitors would therefore be valuable for studying this enzyme and as potential therapeutic agents. Here we present a combined computational/experimental study characterizing 13 nonhydrolyzable ATP analogues selective human inhibitors. All at 100 μM inhibited (66-99%) the hydrolysis of pnp-TMP by both recombinant cell surface...
The effects of phloretin a phytoalexin from apple, was tested on Pectobacterium brasiliense (Pb1692), an emerging soft-rot pathogen potato. Exposure Pb1692 to 0.2 mM concentration that does not affect growth, or 0.4 50% growth inhibiting (50% MIC), reduced motility, biofilm formation, secretion plant cell wall-degrading enzymes, production acyl–homoserine lactone (AHL) signaling molecules and infection, phenotypes are associated with bacterial population density-dependent system known as...
Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the cystic transmembrane conductance regulator (CFTR) chloride channel. The first nucleotide-binding domain (NBD1) of CFTR considered to be a hotspot for CF-causing mutations, and some these compromise domain's thermal stability as well its interactions with other domains. mechanisms which such exert their deleterious effects are important basic research this complex development mutation-specific therapies....
In this paper we extend our previously reported parameterization of carbohydrates to an all-atom AMBER-like force field suitable for modeling oligosaccharides. Parameters were developed from ab initio calculations on small model systems having structures characteristic 1,2-, 1,3-, and 1,4-glycosidic linkages monosaccharides give a complete parameter set pyranose mono- The accuracy the was assessed by free energy various simple sugars disaccharides. Solvent effects included using GB/SA...
In the battle between bacteria and plants, often use a population density-dependent regulatory system known as quorum sensing (QS) to coordinate virulence gene expression. response, plants innate induced defense mechanisms that include low-molecular-weight compounds, some of which serve antivirulence agents by interfering with QS machinery. The best-characterized is driven autoinducer N-acyl-homoserine lactone (AHL), produced AHL synthases (LuxI homologs) perceived response regulators (LuxR...
We describe a novel, potent peptide substrate mimetic inhibitor of protein kinase B (PKB/Akt). The compound selectively kills prostate cancer cells, in which PKB is highly activated, but not normal or cells activated. induces apoptosis and inhibits the phosphorylation substrates cell lines significantly increases efficacy chemotherapy agents to induce death, when given combination. In vivo, exhibits strong antitumor effect two mouse models. Moreover, treated animals develop less lung...