A5065353728- Computational Drug Discovery Methods
- Microbial Natural Products and Biosynthesis
- Metabolomics and Mass Spectrometry Studies
- Protein Structure and Dynamics
- Machine Learning in Materials Science
- Pharmacogenetics and Drug Metabolism
- Influenza Virus Research Studies
- Microbial Metabolic Engineering and Bioproduction
- Plant biochemistry and biosynthesis
- Analytical Chemistry and Chromatography
- Contact Dermatitis and Allergies
- RNA and protein synthesis mechanisms
- Chemical Synthesis and Analysis
- Cholinesterase and Neurodegenerative Diseases
- Protein Kinase Regulation and GTPase Signaling
- Respiratory viral infections research
- Monoclonal and Polyclonal Antibodies Research
- Pharmacological Effects of Natural Compounds
- Chemical synthesis and alkaloids
- Bioinformatics and Genomic Networks
- Herbal Medicine Research Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- PI3K/AKT/mTOR signaling in cancer
- Innovative Microfluidic and Catalytic Techniques Innovation
University of Vienna
2019-2025
Universität Hamburg
2015-2024
Christian Doppler Laboratory for Thermoelectricity
2023-2024
University of Bergen
2018-2023
University of Cambridge
2010-2021
Universidad de Cuautitlán Izcalli
2019
Universidad Nacional Autónoma de México
2019
Instituto Politécnico Nacional
2019
Center for Research and Advanced Studies of the National Polytechnic Institute
2019
Universität Innsbruck
2005-2017
Shape-based molecular similarity approaches have been established as important and popular virtual screening techniques. Recent applications shown successful campaigns using different parameters query selection. It is common sense that pure volume overlap scoring (or "shape-based screening") under-represents chemical or pharmacophoric information of a molecule. Using the "Directory Useful Decoys" (DUD) benchmark set, we systematically evaluate how (i) choice conformations, (ii) selection...
We assess and compare the performance of eight commercial conformer ensemble generators (ConfGen, ConfGenX, cxcalc, iCon, MOE LowModeMD, Stochastic, Conformation Import, OMEGA) one leading free algorithm, distance geometry algorithm implemented in RDKit. The comparative study is based on a new version Platinum Diverse Dataset, high-quality benchmarking dataset 2859 protein-bound ligand conformations extracted from PDB. Differences algorithms are much smaller than those observed for our...
Natural products remain one of the most productive sources chemical inspiration for development new drugs. The structures more than 250 000 natural are available from public databases. At least 10% these compounds readily obtainable experimental testing commercial vendors and research institutions. While physicochemical properties known have been thoroughly studied compared to those drugs other types small molecules, information on content, coverage, relevance individual virtual physical...
Predicting the structures of metabolites formed in humans can provide advantageous insights for development drugs and other compounds. Here we present GLORYx, which integrates machine learning-based site metabolism (SoM) prediction with reaction rule sets to predict rank that could potentially be by phase 1 and/or 2 metabolism. GLORYx extends approach from our previously developed tool GLORY, predicted metabolite cytochrome P450-mediated only. A robust ranking is attained using SoM...
Assay interference caused by small molecules continues to pose a significant challenge for early drug discovery. A number of rule-based and similarity-based approaches have been derived that allow the flagging potentially "badly behaving compounds", "bad actors", or "nuisance compounds". These compounds are typically aggregators, reactive compounds, and/or pan-assay (PAINS), many them frequent hitters. Hit Dexter is recently introduced machine learning approach predicts hitters independent...
We developed a cheminformatics pipeline for the fully automated selection and extraction of high-quality protein-bound ligand conformations from X-ray structural data. The evaluates validity accuracy 3D structures small molecules according to multiple criteria, including their fit electron density physicochemical properties. Using this approach, we compiled two datasets Protein Data Bank (PDB): comprehensive dataset diversified subset 4626 2912 structures, respectively. were applied...
In this work we present the third generation of FAst MEtabolizer (FAME 3), a collection extra trees classifiers for prediction sites metabolism (SoMs) in small molecules such as drugs, druglike compounds, natural products, agrochemicals, and cosmetics. FAME 3 was derived from MetaQSAR database ( Pedretti et al. J. Med. Chem. 2018 , 61 1019 ), recently published data resource on xenobiotic that contains more than 2100 substrates annotated with 6300 experimentally confirmed SoMs related to...
In this study, an integrated in silico–in vitro approach was employed to discover natural products (NPs) active against SARS-CoV-2. The two SARS-CoV-2 viral proteases, i.e., main protease (Mpro) and papain-like (PLpro), were selected as targets for the silico study. Virtual hits obtained by docking more than 140,000 NPs NP derivatives available in-house from commercial sources, 38 virtual experimentally validated using enzyme-based assays. Five inhibited enzyme activity of Mpro 60% at a...
Abstract Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1’s transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 role in signalling remains elusive. Here we demonstrate that interacts directly with a binding motif within CTAR2. Functional NMR studies supported molecular modeling...
We examined the quality of Catalyst's conformational model generation algorithm via a large scale study based on crystal structures sample 510 pharmaceutically relevant protein−ligand complexes extracted from Protein Data Bank (PDB). Our results show that tested algorithms implemented within Catalyst are able to produce high conformers, which in most cases well suited for silico drug research. Catalyst-specific settings were analyzed, such as method used (FAST vs BEST) and maximum number...
A highly efficient conformer search algorithm based on a divide-and-conquer and recursive build-up approach is presented in this paper. This combined with consideration of local rotational symmetry so that duplicates due to topological the systematic can be efficiently eliminated. new algorithm, termed CAESAR (Conformer Algorithm Energy Screening Recursive Buildup), has been implemented Discovery Studio 1.7 as part Catalyst Component Collection. validated by comparing models generated method...
At present, neuraminidase (NA) inhibitors are the mainstay of pharmacological strategies to fight against global pandemic influenza. In search for new antiviral drug leads from nature, seed extract Alpinia katsumadai has been phytochemically investigated. Among six isolated constituents, four diarylheptanoids showed in vitro NA inhibitory activities low micromolar ranges human influenza virus A/PR/8/34 subtype H1N1. The most promising constituent, katsumadain A (4; IC50 = 1.05 ± 0.42 μM),...
Abstract Influenza virus neuraminidase (NA) is the primary target for influenza therapeutics. Severe complications are often related to secondary pneumonia caused by Streptococcus pneumoniae (pneumococci), which also express NAs. Recently, a NA-mediated lethal synergism between A viruses and pneumococci was described. Therefore, dual inhibitors of both viral bacterial NAs expected be advantageous treatment influenza. We investigated traditional Chinese herbal drug sāng bái pí (mulberry root...
Computational prediction of xenobiotic metabolism can provide valuable information to guide the development drugs, cosmetics, agrochemicals, and other chemical entities. We have previously developed FAME 2, an effective tool for predicting sites (SoMs). In this work, we focus on structures metabolites, in particular metabolites xenobiotics. To end, a new tool, GLORY, which combines SoM with 2 collection rules metabolic reactions mediated by cytochrome P450 enzyme family. GLORY has two modes:...