A5063348128- Biochemical and Molecular Research
- Trypanosoma species research and implications
- HIV/AIDS drug development and treatment
- RNA and protein synthesis mechanisms
- Psychedelics and Drug Studies
- Research on Leishmaniasis Studies
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- Receptor Mechanisms and Signaling
- X-ray Diffraction in Crystallography
- Chemical synthesis and alkaloids
- Tryptophan and brain disorders
- Advanced NMR Techniques and Applications
- RNA modifications and cancer
- Pneumocystis jirovecii pneumonia detection and treatment
- Chemical Synthesis and Analysis
- Pharmacological Receptor Mechanisms and Effects
- Chemical Reactions and Isotopes
- Magnetic and Electromagnetic Effects
- Parasitic Infections and Diagnostics
- Steroid Chemistry and Biochemistry
- Crystallography and Radiation Phenomena
- Treatment of Major Depression
- Cyclopropane Reaction Mechanisms
- Veterinary medicine and infectious diseases
Stanford University
2021-2024
University of Washington
2016-2020
Seattle University
2020
University of the Andes
2011-2017
Universidad de Los Andes
2014-2015
AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 of the σ
Abstract AlphaFold2 (AF2) and RosettaFold have greatly expanded the number of structures available for structure-based ligand discovery, even though retrospective studies cast doubt on their direct usefulness that goal. Here, we tested unrefined AF2 models prospectively , comparing experimental hit-rates affinities from large library docking against vs same screens targeting receptors. In σ 2 5-HT2A receptors, struggled to recapitulate ligands had previously found receptors’ structures,...
ABSTRACT Antibiotic-resistant bacteria are widespread and pose a growing threat to human health. New antibiotics acting by novel mechanisms of action needed address this challenge. The bacterial methionyl-tRNA synthetase (MetRS) enzyme is essential for protein synthesis, the type found in Gram-positive substantially different from its counterpart mammalian cytoplasm. Both previously published new selective inhibitors were shown be highly active against with MICs ≤1.3 μg/ml Staphylococcus ,...
Human African trypanosomiasis is a neglected tropical disease that lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from high-throughput screen of >42,000 compounds as highly potent fast-acting trypanocidal agent capable curing bloodstream infection Trypanosoma brucei in mice. We designed library...
Potent <italic>T. brucei</italic> methionyl-tRNA synthetase inhibitors built on two novel short and rigid linker systems.
Mycobacterium tuberculosis is a pathogenic bacterial infectious agent that responsible for approximately 1.5 million human deaths annually. Current treatment requires the long-term administration of multiple medicines with substantial side effects. Lack compliance, together other factors, has resulted in worrisome increase resistance. New options are therefore urgently needed. Here, crystal structure methionyl-tRNA synthetase (MetRS), an enzyme critical protein biosynthesis and drug target,...
Serotonin (5-hydroxytryptamine; 5-HT) 5-HT2-family receptors represent essential targets for the prototypical psychedelic LSD and all other drugs. Although canonical signaling pathway 5-HT2 is mediated by Gq protein activation, pathways β-arrestin recruitment appear actions of in vitro vivo. To gain comprehensive molecular insights into mechanisms LSD, we determined cryoEM structures LSD-bound 5-HT2BR transducer-free, protein-coupled β-arrestin-1-coupled states. These provide distinct...