A5026017430- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Protein Structure and Dynamics
- Microbial Natural Products and Biosynthesis
- Cholinesterase and Neurodegenerative Diseases
- Molecular spectroscopy and chirality
- Microbial Metabolism and Applications
- Biomedical Text Mining and Ontologies
- Machine Learning in Bioinformatics
- Genetics, Bioinformatics, and Biomedical Research
- Machine Learning in Materials Science
- Receptor Mechanisms and Signaling
- Malaria Research and Control
- Mosquito-borne diseases and control
- Protein Degradation and Inhibitors
- Chemical synthesis and alkaloids
- Innovative Microfluidic and Catalytic Techniques Innovation
- Metabolomics and Mass Spectrometry Studies
- Pancreatic function and diabetes
- Pharmacogenetics and Drug Metabolism
- Antibiotic Resistance in Bacteria
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Pharmaceutical and Antibiotic Environmental Impacts
National Center for Advancing Translational Sciences
2018-2024
National Institutes of Health
2018-2021
University of New Mexico
2016-2020
Eötvös Loránd University
2009-2011
Heidelberg University
2010
la diffusion de documents scientifiques niveau recherche, publiés ou non, émanant des établissements d'enseignement et recherche français étrangers, laboratoires publics privés.
Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover complex relationships between them. Here, we introduce an approach which is able relate drug–protein interaction with profiles. Structural data and registered all small-molecule were collected, a series nontarget protein binding sites each drug calculated. Statistical...
Abstract Motivation Chemical space embedding methods are widely utilized in various research settings for dimensional reduction, clustering and effective visualization. The maps generated by the process can provide valuable insight to medicinal chemists terms of relationships between structural, physicochemical biological properties compounds. However, these known be difficult interpret, ‘‘landscape’’ on map is prone ‘‘rearrangement’’ when different sets Results In this study we present...
Complex network theory based methods and the emergence of "Big Data" have reshaped terrain investigating structure-activity relationships molecules. This change gave rise to new which need face an important challenge, namely: how restructure a large molecular dataset into that best serves purpose subsequent analyses. With special focus on clustering, our study addresses this open question by proposing data transformation method clustering framework. Using WOMBAT PubChem MLSMR datasets we...
Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving previously isolated or synthesized compounds largely completely untested. To address this issue, the Canvass library natural was assembled, in collaboration with academic industry researchers, quantitative high-throughput screening (qHTS) across a diverse set cell-based biochemical assays. Characterization...
G-protein-gated inwardly rectifying K+ (GIRK) channels are essential effectors of inhibitory neurotransmission in the brain. GIRK have been implicated diseases with abnormal neuronal excitability, including epilepsy and addiction. tetramers composed either same subunit (e.g., homotetramers) or different subunits heterotetramers). Compounds that specifically target subsets vivo lacking. Previous studies shown alcohol directly activates through a hydrophobic pocket located cytoplasmic domain...
Endoplasmic reticulum (ER) dysregulation is associated with pathologies including neurodegenerative, muscular, and diabetic conditions. Depletion of ER calcium can lead to the loss resident proteins in a process termed exodosis. To identify compounds that attenuate redistribution under pathological conditions, we performed quantitative high-throughput screen using Gaussia luciferase (GLuc)-secreted modulated protein (SERCaMP) assay, which monitors secretion ER-resident triggered by...
Abstract Motivation Drug discovery investigations need to incorporate network pharmacology concepts while navigating the complex landscape of drug-target and target-target interactions. This task requires solutions that integrate high-quality biomedical data, combined with analytic predictive workflows as well efficient visualization. SmartGraph is an innovative platform utilizes state-of-the-art technologies such a Neo4j graph-database, Angular web framework, RxJS asynchronous event library...
Innovating on the design and function of chemical bench remains a quintessential challenge ages. It requires deep understanding important role plays in scientific discovery as well first principles approach to addressing gaps how work gets done at bench. This perspective examines one might explore designing creating sustainable new standard for advancing automated chemistry itself. We propose this be by leveraging recent advances laboratory automation whereby integrating latest synthetic,...
Hierarchical clustering methods like Ward's method have been used since decades to understand biological and chemical data sets. In order get a partition of the set, it is necessary choose an optimal level hierarchy by so-called selection algorithm. 2005, new kind hierarchical was introduced Palla et al. that differs in two ways from method: can be on which no full similarity matrix defined produce overlapping clusters, i.e., allow for multiple membership items clusters. These features are...
Abstract Background Various pattern-based methods exist that use in vitro or silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between protein structural characteristics binding sites is still unclear. Our aim was to investigate association virtual drug screening results (calculated free energy values) geometry sites. Molecular Affinity Fingerprints (MAFs) were determined 154 proteins based on their molecular docking 1,255...
In the event of an outbreak due to emerging pathogen, time is essence contain or mitigate spread disease. Drug repositioning one strategies that has potential deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic shown integrating critical data resources drive drug-repositioning studies, involving host–host, host–pathogen, and drug–target interactions, remains a time-consuming effort translates delay in development delivery life-saving therapy. Here, we describe workflow designed...
The first-line treatments for uncomplicated Plasmodium falciparum malaria are artemisinin-based combination therapies (ACTs), consisting of an artemisinin derivative combined with a longer acting partner drug. However, the spread P. decreased susceptibility to and drugs presents significant challenge control efforts. To stem drug resistant parasites, novel chemotherapeutic strategies being evaluated, including implementation triple (TACTs). Currently, there is limited knowledge on...
Synthesis route planning is in the core of chemical intelligence that will power autonomous chemistry platforms. In this task, we rely on algorithms to generate possible synthesis routes with help retro- and forward-synthetic approaches. Generated can be merged into a graph which represents theoretical pathways target molecule. However, it often required modify due typical constraints. These constraints might include "undesirable substances", e.g., an intermediate chemist does not favor or...
The recent SmartGraph platform facilitates the execution of complex drug-discovery workflows with ease in network-pharmacology paradigm. However, at time its publication, we identified need for development an Application Programming Interface (API) that could promote biomedical data integration and hypothesis generation automated manner. This was magnified COVID-19 pandemic. study addresses this hiatus. Most functionalities original were implemented API. We demonstrate by using API it is...
Rapid generation and evaluation of diverse synthesis pathways play a critical role in exploring broader chemical space identifying potent drug candidates. Drug discovery often relies on laborintensive manual processes for retro synthetic route finding, resulting challenges related to scalability reproducibility. Autonomous platforms, like ASPIRE aim address this bottleneck by the development high-throughput capabilities. While AI/ML-based predictive methods exist that can generate routes...
The recent SmartGraph platform facilitates the execution of complex drug-discovery workflows with ease in network-pharmacology paradigm. However, at time its publication we identified need for development an Application Programming Interface (API) that could promote biomedical data integration and hypothesis generation automated manner. This was magnified COVID-19 pandemic. study addresses absence such API. Accordingly, most functionalities original were implemented within We demonstrate by...
Abstract Motivation In the event of an outbreak due to emerging pathogen, time is essence contain or mitigate spread disease. Drug repositioning one strategies that has potential deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic shown integrating critical data resources drive drug-repositioning studies, involving host-host, hostpathogen and drug-target interactions, remains a time-consuming effort translates delay in development delivery life-saving therapy. Results Here, we...