A5033336225- Protein Structure and Dynamics
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- Enzyme Catalysis and Immobilization
- Receptor Mechanisms and Signaling
- Enzyme Structure and Function
- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Photoreceptor and optogenetics research
- Phytochemicals and Antioxidant Activities
- melanin and skin pigmentation
- Biochemical Analysis and Sensing Techniques
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Bioinformatics and Genomic Networks
- Retinal Development and Disorders
- Multiple Myeloma Research and Treatments
- Lipid Membrane Structure and Behavior
- Machine Learning in Materials Science
- Asymmetric Hydrogenation and Catalysis
- Lipid metabolism and biosynthesis
- Nicotinic Acetylcholine Receptors Study
Ewha Womans University
2021-2024
Ewha Womans University Medical Center
2024
University of Girona
2017-2022
University of Regensburg
2021
Clínica Girona
2017
Universidad de Murcia
2015
There have been numerous advances in the development of computational and statistical methods applications big data artificial intelligence (AI) techniques for computer-aided drug design (CADD). Drug is a costly laborious process considering biological complexity diseases. To effectively efficiently develop new drug, CADD can be used to apply cutting-edge various limitations field. Data pre-processing approaches, which clean raw consistent reproducible AI are introduced. We include current...
Deciphering the molecular mechanisms of enzymatic allosteric regulation requires structural characterization functional states and also their time evolution toward formation allosterically activated ternary complex. The transient nature usually slow millisecond scale interconversion between these hamper experimental computational characterization. Here, we combine extensive dynamics simulations, enhanced sampling techniques, dynamical networks to describe activation imidazole glycerol...
Multimeric enzyme complexes are ubiquitous in nature and catalyze a broad range of useful biological transformations. They often characterized by tight allosteric coupling between subunits, making them highly inefficient when isolated. A good example is Tryptophan synthase (TrpS), an heterodimeric the form αββα complex that catalyzes biosynthesis L-tryptophan. In this study, we decipher regulation existing TrpS from Pyrococcus furiosus (PfTrpS), how conformational ensemble recovered...
Allostery is a central mechanism for the regulation of multi-enzyme complexes. The mechanistic basis that drives allosteric poorly understood but harbors key information enzyme engineering. In present study, we focus on tryptophan synthase complex composed TrpA and TrpB subunits, which allosterically activate each other. Specifically, develop rational approach identifying amino acid residues distal from active site. Those are predicted to be crucial shifting inefficient conformational...
Abstract Impaired ion channels regulating Golgi pH lead to structural alterations in the apparatus, such as fragmentation, which is found, along with cognitive impairment, Alzheimer’s disease. However, causal relationship between altered structure and impairment remains elusive due lack of understanding apparatus brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed astrocytes neurons contributes...
Turn cool off and stay active: the thermostable alcohol dehydrogenase TbSADH originating from hot springs of Yellow Stone Park was successfully subjected to directed evolution for inducing high activity at ambient temperatures enabling short reaction times with minimal tradeoff in thermostability. Reversed enantioselectivity also evolved (99% ee).
Machine learning (ML) has pervaded most areas of protein engineering, including stability and stereoselectivity. Using limonene epoxide hydrolase as the model enzyme innov'SAR ML platform, comprising a digital signal process, we achieved high robustness that can resist unfolding with concomitant detrimental aggregation. Fourier transform (FT) allows us to take into account order sequence nonlinear interactions between positions, thus grasp epistatic phenomena. The approach is interpolative,...
Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to corresponding alcohols. These present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate effect commonly reported mutations (I86A, W110T) on a secondary alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics simulations. Our results indicate that introduced induce dramatic...
Abstract The development of effective tyrosinase inhibitors has become increasingly important in the cosmetic, medicinal, and agricultural industries for application as antibrowning depigmenting agents. kinetic mechanisms action on monophenols o ‐diphenols are complex, particularly case because lag period that occurs at beginning reaction. When enzyme studied, problem becomes more complicated increases, which led to erroneous identification type inhibition many compounds exert monophenolase...
G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics is critical for development therapeutics. Here, we target adenosine A 1 (A R), which a negligible number drugs have been approved. We combine molecular simulations, enhanced sampling techniques, network theory, pocket detection to decipher pathway R, decode allosteric networks, identify transient pockets. The R reveals hidden...
Abstract TMEM87 family is evolutionarily conserved eukaryotic transmembrane proteins residing in the Golgi 1 . members play a role retrograde transport and are also proposed mechanosensitive ion channel implicated cancer heart disease 2–7 In an accompanying study, TMEM87A described as voltage-gated, pH-sensitive, non-selective cation whose genetic ablation mice disrupts morphology, alters glycosylation protein trafficking, impairs hippocampal memory. Despite pivotal functions of TMEM87s...
<title>Abstract</title> Impaired ion channels regulating Golgi pH lead to structural alterations in the apparatus, such as fragmentation, which is found, along with cognitive impairment, Alzheimer’s disease. However, causal relationship between altered structure and impairment remains elusive due lack of understanding apparatus brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed astrocytes neurons contributes...
ABSTRACT Proteolysis Targeting Chimeric Molecules (PROTACs) represent a promising avenue in drug discovery, as they can induce the targeted degradation of disease-relevant proteins within cellular machinery. These compounds comprise ligand tailored to bind specific protein connected recruiter molecule that engages with E3 ligase. Despite their promise therapeutic agents, clinical advancement has encountered substantial challenges, primarily due limited availability suitable ligases....
G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics is critical for development therapeutics. Here, we target adenosine A 1 (A R), which a negligible number drugs have been approved. We combine molecular simulations, enhanced sampling techniques, network theory, pocket detection to decipher pathway R, decode allosteric networks, identify transient pockets. The R reveals hidden...
ABSTRACT G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics is critical for development therapeutics. Here, we target adenosine A 1 (A R), which a negligible number drugs have been approved. We combine molecular simulations, enhanced sampling techniques, network theory pocket detection to decipher pathway R, decode allosteric networks identify transient pockets. The R reveal...
Allostery is a central mechanism for the regulation of multi-enzyme complexes. The mechanistic basis that drives allosteric poorly understood, but harbors key information enzyme engineering. In present study, we focus on tryptophan synthase complex composed TrpA and TrpB subunits, which allosterically activate each other. Specifically, develop rational approach identifying amino acid residues distal from active site. particular, predict positions crucial shifting inefficient conformational...
ABSTRACT Deciphering the molecular mechanisms of enzymatic allosteric regulation requires structural characterization key functional states and also their time evolution toward formation allosterically activated ternary complex. The transient nature usually slow millisecond timescale interconversion between these hamper detailed experimental computational characterization. Here, we design a strategy tailored to reconstruct events describe graded activation imidazole glycerol phosphate...
G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics is critical for development therapeutics. Here, we target adenosine A 1 (A R), which a negligible number drugs have been approved. We combine molecular simulations, enhanced sampling techniques, network theory pocket detection to decipher pathway R, decode allosteric networks identify transient pockets. The R reveal hidden...
Allostery is a central mechanism for the regulation of multi-enzyme complexes. The mechanistic basis that drives allosteric poorly understood, but harbors key information enzyme engineering. In present study, we focus on tryptophan synthase complex composed TrpA and TrpB subunits, which allosterically activate each other. Specifically, develop rational approach identifying amino acid residues distal from active site. particular, predict positions crucial shifting inefficient conformational...