A5000452644- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Ion channel regulation and function
- Trace Elements in Health
- Click Chemistry and Applications
- Bipolar Disorder and Treatment
- Radiopharmaceutical Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Photoreceptor and optogenetics research
- Crystallography and molecular interactions
- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Neuropharmacology Research
- Amino Acid Enzymes and Metabolism
- Protein Structure and Dynamics
- Plant nutrient uptake and metabolism
- Metal complexes synthesis and properties
- Influenza Virus Research Studies
- Magnesium in Health and Disease
- Biochemical effects in animals
- Ion Transport and Channel Regulation
- Corrosion Behavior and Inhibition
- Chemical Synthesis and Analysis
Institute of Biological Chemistry, Academia Sinica
2025
Institute of Biomedical Sciences, Academia Sinica
2015-2023
Academia Sinica
2016-2018
Institute of Molecular Biology and Biophysics
2016-2018
National Taiwan University
2016-2018
The COVID-19 pandemic poses a challenge in coming up with quick and effective means to counter its cause, the SARS-CoV-2. Here, we show how key factors governing cysteine reactivity proteins derived from combined quantum mechanical/continuum calculations led novel multi-targeting strategy against SARS-CoV-2, contrast developing potent drugs/vaccines single viral target such as spike protein. Specifically, they discovery of reactive cysteines evolutionary conserved Zn
The hydrogen-bonding interactions of cysteine, which can serve as a hydrogen-bond donor and/or acceptor, play central role in cysteine's diverse functional roles proteins. They affect the balance between neutral thiol (SH) or thiolate (S–) and charge distribution rate-limiting transition state reaction. Despite their importance, no study has determined preferred partners cysteine serving acceptor. By computing free energy for displacing peptide backbone hydrogen-bonded to with amino acid...
Alterations in viral fitness cannot be inferred from only mutagenesis studies of an isolated protein. To-date, no systematic analysis has been performed to identify mutations that improve virus and reduce drug efficacy. We present a generic strategy evaluate which might diminish efficacy applied it assess how SARS-CoV-2 evolution may affect the current approved/candidate small-molecule antivirals for Mpro, PLpro, RdRp. For each target, we determined drug-interacting residues available...
Abstract Voltage-gated proton channels, H V 1, trigger bioluminescence in dinoflagellates, enable calcification coccolithophores and play multifarious roles human health. Because the concentration is minuscule, exquisite selectivity for protons over other ions critical to 1 function. The of open channel requires an aspartate near arginine filter (SF), a narrow region that dictates selectivity, but mechanism unknown. Here we use reduced quantum model elucidate how Asp–Arg SF selects excludes...
Li<sup>+</sup>(turquoise), the better charge acceptor, can displace Na<sup>+</sup>(purple) bound by only one or two aa residues in buried sites. Thus, Li<sup>+</sup>can Na<sup>+</sup>bound Asp<sup>−</sup>and Ser A<sub>2A</sub>AR/β<sub>1</sub>AR receptor and enhance metal site's stability, thus prohibiting structural distortions induced agonist binding, leading to lower cytosolic levels of activated G-proteins, which are hyperactive bipolar disorder patients.
Na(+) and Mg(2+) play different crucial roles in biological systems. Both cations are present comparable amounts the cytosol, but how monovalent can compete with divalent Mg(2+), which better accept charge from negatively charged ligands, sodium transporters/enzymes has not been investigated. Hence, it is clear Mg(2+)-binding sites have evolved to discriminate "right" cation among non-cognate ones surrounding milieu physical basis governing selectivity for over Mg(2+). The results,...
Hydrogen bonds to metal–ligands in proteins play a vital role biological function. They help stabilize/protect the metal complex and enhance metal-binding affinity/specificity, enzyme–substrate recognition, enzyme activation. Yet, knowledge of preferred hydrogen-bonding partners ligands different metalloproteins is lacking. Using well-calibrated methods, we have determined Cys– bound native Zn2+ or xenobiotic Cd2+ Zn-fingers varying net charge solvent accessibility as well key factors...
Strontium (Sr), an alkali metal with properties similar to calcium, in the form of soluble salts is used treat osteoporosis. Despite information accumulated on role Sr2+ as a Ca2+ mimetic biology and medicine, there no systematic study how outcome competition between two dications depends physicochemical (i) ions, (ii) first- second-shell ligands, (iii) protein matrix. Specifically, key features Ca2+-binding that enable displace remain unclear. To address this, we studied sites using density...
Abstract Alterations in viral fitness cannot be inferred from only mutagenesis studies of an isolated protein. To-date, no systematic analysis has been performed to identify mutations that improve virus and reduce drug efficacy. We present a generic strategy evaluate which will diminish efficacy applied it assess how SARS-CoV-2 evolution may affect the current approved/candidate small-molecule antivirals for M pro , PL RdRp. For each target, we determined drug-interacting residues available...
Abstract Alterations in viral fitness cannot be inferred from only mutagenesis studies of an isolated protein. To-date, no systematic analysis has been performed to identify mutations that improve virus and reduce drug efficacy. We present a generic strategy evaluate which will diminish efficacy applied it assess how SARS-CoV-2 evolution may affect the current approved/candidate small-molecule antivirals for Mpro, PLpro, RdRp. For each target, we determined drug-interacting residues...
Broad-spectrum antivirals that work against many viruses provide an immediate treatment for diseases caused by novel pathogenic viruses. Notably, there is no universal drug all four genera of the coronaviridae family, in particular d-coronaviruses, which have recently spilled over from pigs to humans. Here, we present and illustrate in-silico strategy evaluate potential broad-spectrum activity EUA-approved drug; viz., nirmatrelvir, porcine d-coronavirus (PDCoV) has infected First, show...