A5044322881- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Synthesis and biological activity
- Chemokine receptors and signaling
- Cancer therapeutics and mechanisms
- Drug Transport and Resistance Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Sphingolipid Metabolism and Signaling
- Cancer Mechanisms and Therapy
- Receptor Mechanisms and Signaling
- ATP Synthase and ATPases Research
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Cancer-related Molecular Pathways
- Bioinformatics and Genomic Networks
- Microtubule and mitosis dynamics
- Phagocytosis and Immune Regulation
- Pharmacological Effects of Natural Compounds
- HIV/AIDS drug development and treatment
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- Chronic Lymphocytic Leukemia Research
- Protein Structure and Dynamics
Chungnam National University
2017-2024
Chosun University
2013-2019
Institute of Biomedical Science
2015
National Institute of Pharmaceutical Education and Research
2012-2014
Gwangju University
2014
Abstract The α-synuclein is a major component of amyloid fibrils found in Lewy bodies, the characteristic intracellular proteinaceous deposits which are pathological hallmarks neurodegenerative diseases such as Parkinson’s disease (PD) and dementia. It an intrinsically disordered protein that may undergo dramatic structural changes to form fibrils. Aggregation process from monomers through oligomeric intermediates considered disease-causative toxic mechanism. However, mechanism underlying...
Janus kinase 3 (JAK3) is a promising drug target for the treatment of inflammatory diseases, autoimmune disorders, organ transplant rejection and various cancers. In present study, 3D-QSAR, docking, MD simulation MM/PBSA studies were performed on series pyrimidine-based JAK3 inhibitors. A reliable COMSIA (q2 = 0.717 r2 0.986) model was developed validated using external validation test set, bootstrapping, progressive scrambling rm2 metrics analyses. Structural requirements identified through...
Human ether-a-go-go-related gene (hERG) potassium channel blockage by small molecules may cause severe cardiac side effects. Thus, it is crucial to screen compounds for activity on the hERG channels early in drug discovery process. In this study, we collected 5299 inhibitors with diverse chemical structures from a number of sources. Based dataset, evaluated different machine learning (ML) and deep (DL) algorithms using various integer binary type fingerprints. A training set 3991 was used...
We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer's disease (AD). (2R)-Pterosin B BACE1, acetylcholinesterase (AChE) butyrylcholinesterase (BChE) with an IC50 29.6, 16.2 48.1 µM, respectively. The Ki values binding energies (kcal/mol) between pterosins AChE, BChE corresponded to respective values. was a noncompetitive inhibitor against human...
Human CC-chemokine receptor 8 (CCR8) is a crucial drug target in asthma that belongs to G-protein-coupled superfamily, which characterized by seven transmembrane helices. To date, there no X-ray crystal structure available for CCR8; this hampers active research on the target. Molecular basis of interaction mechanism antagonist with CCR8 remains unclear. In order provide binding site information and stable mode, we performed modeling, docking molecular dynamics (MD) simulation CCR8. Docking...
Bruton tyrosine kinase (Btk) plays an important role in B-cell development, differentiation, and signaling. It is also found be involved male immunodeficiency disease such as X-linked agammaglobulinemia (XLA). Btk considered a potential therapeutic target for treating autoimmune diseases hematological malignancies.In this work, combined molecular modeling study was performed on series of thieno [3,2-c] pyridine-4-amine derivatives inhibitors. Receptor-guided COMFA (q 2 = 0.574, NOC 3, r...
Sauchinone, an active lignan isolated from the aerial parts of Saururus chinensis (Saururaceae), exhibits anti-inflammatory, anti-obesity, anti-hyperglycemic, and anti-hepatic steatosis effects. As herb-drug interaction (HDI) through cytochrome P450s (CYPs)-mediated metabolism limits clinical application herbs drugs in combination, this study sought to explore enzyme kinetics sauchinone towards CYP inhibition vitro human liver microsomes (HLMs) vivo mice studies computational molecular...
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and a widespread form dementia. Aggregated forms amyloid β-peptide (Aβ) are identified as toxic species responsible for neuronal damage in AD. Extensive research has been conducted to reveal aggregation mechanism Aβ. However, structure pathological aggregates not well understood. Recently, experimental studies have confirmed that α-sheet Aβ drives toxicity how formed it contributes remains elusive. In present...
Mesenchymal-epithelial transition factor (c-Met) is a member of receptor tyrosine kinase. It involves in various cellular signaling pathways which includes proliferation, motility, migration, and invasion. Over-expression c-Met has been reported cancers. Hence, it an ideal therapeutic target for cancer. The main objective the study to identify crucial residues involved inhibition kinase design series potent imidazo [4,5-b] pyrazine derivatives as inhibitors. Docking was used important active...
Checkpoint kinase 1 (Chk1) is a promising target for the design of novel anticancer agents. In present work, molecular docking simulations and three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on pyridyl aminothiazole derivatives as Chk1 inhibitors. AutoDock was used to determine probable binding conformations all compounds inside active site Chk1. Comparative field analysis (CoMFA) comparative similarity indices (CoMSIA) models developed based...
In order to elucidate the essential structural features for CC chemokine receptor 2 (CCR2) antagonism, 3D-pharmacophore hypotheses were built based on a set of known compounds from literature. The developed with aid HypoGen module within Discovery Studio 2.5 program. Multiple validation approaches provided confidence in utilising predictive pharmacophore models this study. most model (Hypo1) was found be statistically significant along its ability predict activities CCR2 antagonists training...
Water molecules play a key role in protein stability, folding, function and ligand binding. Protein hydration has been studied using free energy perturbation algorithms. However, the study of without calculation is also an active field research. Accordingly, topological water network (TWN) analysis carried out instead present work to investigate proteins. networks around 20 amino acids aqueous solution were explored through molecular dynamics (MD) simulations. These simulation results...
Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a protein with diverse functions in cell regulation. Abnormal expression and activity of DYRK1A contribute to numerous human malignancies, Down syndrome, Alzheimer’s disease. Notably, has been proposed as potential therapeutic target for the treatment diabetes because its key role pancreatic β-cell proliferation. Consequently, an attractive drug variety diseases. Here, we report identification several inhibitors using...
Protein kinases are deeply involved in immune-related diseases and various cancers. They a potential target for structure-based drug discovery, since the general structure characteristics of kinase domains relatively well-known. However, ATP binding sites protein kinases, which serve as sites, highly conserved, thus it is difficult to develop selective inhibitors. To resolve this problem, we performed molecular dynamics simulations on 26 aqueous solution, analyzed topological water networks...
The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of virus into host cells. crucial suggests as potential drug target for future antiviral therapies. Identification binding mode small like compounds has been an important goal design. In current study we attempt to propose indole derivatives pocket gp120. These are reported inhibit by acting attachment inhibitors that bind and prevent gp120-CD4 interaction thus infectivity HIV-1. To elucidate molecular basis molecules...
The nociceptin receptor (NOPR) is an orphan G protein-coupled that contains seven transmembrane helices.
The (c-Jun N-terminal kinase 3) JNK3 is a potential therapeutic target for various neurological disorders. Here, three dimensional quantitative structure-activity relationship (3D-QSAR) study on phenoxypyridine as inhibitors was performed to rationalize the structural requirements responsible inhibitory activity of these compounds. comparative molecular field analysis (CoMFA) using different partial atomic charges, employed understand factors affecting potency. Gasteiger-Marsili yielded...
Autotaxin (ATX) is a potential drug target that associated with inflammatory diseases and various cancers. In our previous studies, we have designed several inhibitors targeting ATX using computational experimental approaches. Here, analyzed topological water networks (TWNs) in the binding pocket of ATX. TWN analysis revealed pharmacophoric site inside pocket. We synthesized compounds considering identified site. Furthermore, performed biological experiments to determine their inhibitory...