A5045868274- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Organophosphorus compounds synthesis
- Chemical Reaction Mechanisms
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Phosphorus compounds and reactions
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Reactions
- DNA and Nucleic Acid Chemistry
- Peptidase Inhibition and Analysis
- Analytical Chemistry and Chromatography
- RNA and protein synthesis mechanisms
- Nanoparticle-Based Drug Delivery
- Free Radicals and Antioxidants
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Metabolomics and Mass Spectrometry Studies
- Chemical Synthesis and Characterization
- Cholinesterase and Neurodegenerative Diseases
- Chemical Reactions and Mechanisms
- Click Chemistry and Applications
- Organic Chemistry Cycloaddition Reactions
- Advanced Chemical Physics Studies
- Pharmacogenetics and Drug Metabolism
- Inorganic and Organometallic Chemistry
Hebrew University of Jerusalem
2013-2024
University of Missouri
2024
Universidade Federal de Viçosa
2022
Universidade Federal de Minas Gerais
2022
Omsk State Technical University
2022
Fujian Normal University
2022
Leipzig University
2022
Tel Aviv University
2002
University of Cambridge
2002
PharmChem (United States)
1988-1990
Abstract ‘Drug‐likeness’, a qualitative property of chemicals assigned by experts committee vote, is widely integrated into the early stages lead and drug discovery. Its conceptual evolution paralleled work related to Pfizer's ‘rule five’ lead‐likeness, placed within this framework. The discrimination between ‘drugs’ (represented collection pharmaceutically relevant small molecules, some which are marketed drugs) ‘nondrugs’ (typically, chemical reagents) possible using wide variety...
Glycogen branching enzyme 1 (GBE1) plays an essential role in glycogen biosynthesis by generating α-1,6-glucosidic branches from α-1,4-linked glucose chains, to increase solubility of the polymer. Mutations GBE1 gene lead heterogeneous early-onset storage disorder type IV (GSDIV) or late-onset adult polyglucosan body disease (APBD). To better understand this enzyme, we crystallized human apo form, and complex with a tetra- hepta-saccharide. The structure reveals conserved amylase core that...
Acylphosphonic acids (5) and methyl hydrogen acylphosphonates (3) were synthesized by di- mono-demethylation of dimethyl (1). Spectroscopic data (i.r., 31P 1H n.mr.) are reported for these types compounds the first time. Examination their hydrolytic stability under acidic basic conditions revealed that except unstable highly alkaline pH conditions, C–P bond in is stable most cases. Nucleophilic reagents, e.g. amines, borohydride, or hydroxylamine react with carbonyl group ionized...
Abstract The molecular electrostatic potentials computed by the overlap‐multipole‐expansion procedure ( OMTP ) are compared to exact with same Gaussian basis set, for different species. It is shown that at distances of molecule larger than 2.2 Å, values those ones within an error 0.5 kcal/mol. This decreases increasing distance. For below this limit may be used as a first indication trends molecule, provided compare not too close.
Abstract Recent suggestions for correcting HAcceptor interactions within MNDO, together with results of crystallographic analysis, were used to modify this SCF semiempirical calculation multiple hydrogen bonded associations. Thermodynamic profiles model systems biochemical interest such as H 2 OH O, hydration neutral and charged molecules, dimerizations proton transfers show the advantages method. Its treatment charges, bonding, geometries, energetics vibrational frequencies is shown be...
Abstract Multiple near‐optimal conformations of protein‐ligand complexes provide a better chance for accurate representation biomolecular interactions, compared with single structure. We present ISE‐dock – docking program which is based on the iterative stochastic elimination (ISE) algorithm. ISE eliminates values that consistently lead to worst results, thus optimizing search poses. It constructs large sets such poses no additional computational cost validated using 81 from PDB and its...
PPAR-δ agonists are known to enhance fatty acid metabolism, preserving glucose and physical endurance suggested as candidates for treating metabolic diseases. None have reached the clinic yet. Our Machine Learning algorithm called "Iterative Stochastic Elimination" (ISE) was applied construct a ligand-based multi-filter ranking model distinguish between confirmed random molecules. Virtual screening of 1.56 million molecules by this picked ~2500 top Subsequent docking structures mainly...
Alzheimer's disease (AD) is a complex and widespread condition, still not fully understood with no cure yet. Amyloid beta (Aβ) peptide suspected to be major cause of AD, therefore, simultaneously blocking its formation aggregation by inhibition the enzymes BACE-1 (β-secretase) AChE (acetylcholinesterase) single inhibitor may an effective therapeutic approach, as compared one these targets or combining two drugs, for each targets. We used our ISE algorithm model peripheral site inhibitors...
Dragline spider silk fibers have extraordinary attributes as biomaterials of superior strength and toughness. Previously we shown that the conserved C-terminal domain a dragline protein is necessary for directing oriented microfiber formation. Here present first time state-of-the-art model three-dimensional structure this domain, and, by comparing several proteins, identify its key evolutionarily features. Further, using baculovirus expression system, produced recombinant proteins are...
Toll-like receptors (TLR) are of innate immunity that recognize pathogen associated molecular patterns. They play a critical role in many pathological states, acute and chronic inflammatory processes. TLR9 is promising target for drug discovery, since it has been implicated several pathologies, including defense against viral infections psoriasis. Immune-modulators molecules therapeutic intervention these indications. located the endosome activated by dsDNA with CpG motives encountered...
G protein-coupled receptors (GPCRs) are targets of many drugs, which ∼25% indicated for central nervous system (CNS) disorders. Drug promiscuity affects their efficacy and safety profiles. Predicting the polypharmacology profile compounds against GPCRs can thus provide a basis producing more precise therapeutics by considering anti-targets in that family closely related proteins. We tool predicting within prominent GPCR families CNS: serotonin, dopamine, histamine, muscarinic, opioid,...
The problem of global optimization is pivotal in a variety scientific fields. Here, we present robust stochastic search method that able to find the minimum for given cost function, as well as, most cases, any number best solutions very large combinatorial “explosive” systems. algorithm iteratively eliminates variable values contribute consistently highest end function's spectrum full system. Values have not been eliminated are retained full, exhaustive search, allowing creation an ordered...
Dialkyl α-oxyiminoalkylphosphonates, obtained by treatment of dialkyl acylphosphonates with hydroxylamine or methoxylamine, are mostly mixtures E and Z isomers. Structural assignments the oximes were based on X-ray crystallographic analysis representative compounds: (E)- (Z)-dimethyl α-hydroxyiminobenzylphosphonates [(E)- (Z)-(1a)]. The 31P n.m.r. chemical shifts isomers always appear at lower field than those corresponding Thermal fragmentation (1a) affords benzonitrile dimethyl hydrogen...
Integration of computational methods in the early stages drug discovery has been one key trends pharmaceutical industry. Starting with high quality candidates should ultimately minimize clinical attrition rates and give rise to higher success rates. In this paper, we present a novel approach for indexing oral druglikeness compounds. With Iterative Stochastic Elimination (ISE) Algorithm, distinguish between orally available drugs nondrugs by generating sets optimized descriptors' ranges, each...