• Journal of Integrative Natural Science
• /
• 제11권1호
• /
• pp.25-29
• /
• 2018

Protein phosphatase manganese dependent 1D (PPM1D), a Ser/Thr protein phosphatise, play major role in the cancer tumorigenesis of various tumors including neuroblastoma, pancreatic adenocarcinoma, medulloblastoma, breast cancer, prostate cancer and ovarian cancer. Hence, analysis on the structural features required for the formation of PPM1D-inhibitor complex becomes essential. In this study, we have performed molecular docking of SL-175 and -176 and protein-protein docking of CDC5L with PPM1D. On analysing the docked complexes, we have identified the important residues involved in the formation of protein-ligand complex. Research concentrating on these residues could be helpful in understanding the pathophysiology of various tumors related to PPM1D.

• Bulletin of the Korean Chemical Society
• /
• 제32권4호
• /
• pp.1241-1248
• /
• 2011

Three dimensional quantitative structure-activity relationships (3D-QSARs) between new thiosemicarbazone analogues (1-31) as a substrate molecule and their inhibitory activity against tyrosinase as a receptor were performed and discussed quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods. According to the optimized CoMSIA 2 model obtained from the above procedure, inhibitory activities were mainly dependent upon H-bond acceptor favored field (36.5%) of substrate molecules. The optimized CoMSIA 2 model, with the sensitivity of the perturbation and the prediction, produced by a progressive scrambling analysis was not dependent on chance correlation. From molecular docking studies, it is supposed that the inhibitory activation of the substrate molecules against tyrosinase (PDB code: 1WX2) would not take place via uncompetitive inhibition forming a chelate between copper atoms in the active site of tyrosinase and thiosemicarbazone moieties of the substrate molecules, but via competitive inhibition based on H-bonding.

• Bulletin of the Korean Chemical Society
• /
• 제32권7호
• /
• pp.2433-2442
• /
• 2011

The three dimensional quantitative structure activity relationship (3D QSAR) models were developed using Comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking studies. The fit of Quinazolinone antifolates inside the active site of modeled bovine dihydrofolate reductase (DHFR) was assessed. Both ligand based (LB) and receptor based (RB) QSAR models were generated, these models showed good internal and external statistical reliability that is evident from the $q^2_{loo}$, $r^2_{ncv}$ and $r^2_{pred}$. The identified key features enabled us to design new Quinazolinone analogues as DHFR inhibitors. This study is a building bridge between docking studies of homology modeled bovine DHFR protein as well as ligand and target based 3D QSAR techniques of CoMFA and CoMSIA approaches.

• The Journal of the Korea Contents Association
• /
• 제8권12호
• /
• pp.441-448
• /
• 2008

The molecular docking system needs a large amount of computation and requires super-computing power. Since the experiment requires a large amount of time, the experiment is conducted in the distributed environment or in the grid environment. Recently, researches on using parallel GPU of far higher performance than that of CPU in scientific computing have been very actively conducted. CUDA is an open technique by which a parallel GPU programming is made possible. This study proposes the molecular docking system using CUDA. It also proposes algorithm that parallels energy-minimizing-computation. To verify such experiments, this study conducted a comparative analysis on the time required for experimenting molecular docking in general CPU and the time and performance of the parallel GPU-based molecular docking which is proposed in this study.

• Bulletin of the Korean Chemical Society
• /
• 제24권1호
• /
• pp.95-98
• /
• 2003

Enantioselectivity of the propranolol on β-cyclodextrin was simulated by molecular modeling. Monte Carlo (MC) docking and molecular dynamics (MD) simulations were applied to investigate the molecular mechanism of enantioselective difference of both enantiomeric complexes. An energetic analysis of MC docking simulations coupled to the MD simulations successfully explains the experimental elution order of propranolol enantiomers. Molecular dynamics simulations indicate that average energy difference between the enantiomeric complexes, frequently used as a measure of chiral recognition, depends on the length of the simulation time. We found that, only in case of much longer MD simulations, noticeable chiral separation was observed.

• Bulletin of the Korean Chemical Society
• /
• 제27권2호
• /
• pp.266-272
• /
• 2006

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.

• Journal of Microbiology and Biotechnology
• /
• 제33권2호
• /
• pp.268-276
• /
• 2023

Alkyl butyrate with fruity flavor is known as an important additive in the food industry. We synthesized various alkyl butyrates from various fatty alcohol and butyric acid using immobilized Rhodococcus cutinase (Rcut). Esterification reaction was performed in a non-aqueous system including heptane, isooctane, hexane, and cyclohexane. As a result of performing the alkyl butyrate synthesis reaction using alcohols of various chain lengths, it was found that the preference for the alcohol substrate had the following order: C6 > C4 > C8 > C10 > C2. Through molecular docking analysis, it was found that the greater the hydrophobicity of alcohol, the higher the accessibility to the active site of the enzyme. However, since the number of torsions increased as the chain length increased, it became difficult for the hydroxyl oxygen of the alcohol to access the ^γO of serine at the enzyme active site. These molecular docking results were consistent with substrate preference results of the Rcut enzyme. The Rcut maintained the synthesis efficiency at least for 5 days in isooctane solvent. We synthesized as much as 452 mM butyl butyrate by adding 100 mM substrate daily for 5 days and performing the reaction. These results show that Rcut is an efficient enzyme for producing alkyl butyrate used in the food industry.

• Journal of Integrative Natural Science
• /
• 제7권3호
• /
• pp.159-165
• /
• 2014

Pyrazole, hydroxyimino, aldehyde and isoxazole derivatives exhibit a broad spectrum of biological activities such as antimicrobial, anti-inflammatory and antitumor activities. With growing application on their synthesis and bioactivity, chemists and biologists in recent years have considerable attention on the research of these derivatives. In the view of potential importance of these derivatives, we have crystallized few of the derivatives and its report has been published. The present study focuses on docking studies of these derivatives against Phospholipases $A_2$ enzyme. This enzymes has implicated as potential targets for anti-inflammatory drug design. co-crystal structure (PDB ID: 1POE) of $PLA_2$ deposited in Protein Data Bank has been retrieved for docking analysis. Docking studies using Schrodinger's GLIDE reveals that these derivatives shows better binding energy and score in the defined active site. These results may provide a guiding role to design a lead molecule which may reduce inflamation.

• Genomics & Informatics
• /
• 제12권2호
• /
• pp.64-70
• /
• 2014

Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The life-threatening infection caused by HPV demands the need for designing anticancerous drugs. In the recent years, different compounds from natural origins, such as carrageenan, curcumin, epigallocatechin gallate, indole-3-carbinol, jaceosidin, and withaferin, have been used as a hopeful source of anticancer therapy. These compounds have been shown to suppress HPV infection by different researchers. In the present study, we explored these natural inhibitors against E6 oncoprotein of high-risk HPV-16, which is known to inactivate the p53 tumor suppressor protein. A robust homology model of HPV-16 E6 was built to anticipate the interaction mechanism of E6 oncoprotein with natural inhibitory molecules using a structure-based drug designing approach. Docking analysis showed the interaction of these natural compounds with the p53-binding site of E6 protein residues 113-122 (CQKPLCPEEK) and helped the restoration of p53 functioning. Docking analysis, besides helping in silico validation of natural compounds, also helps understand molecular mechanisms of protein-ligand interactions.

• Journal of Industrial and Engineering Chemistry
• /
• 제67권
• /
• pp.293-300
• /
• 2018

Lipocalins are diverse group of small extracellular proteins found in various organisms. In this study, members of 10 non-homologous lipocalin-ligand crystal complex structures were remodeled using rigid and flexible ligand modes to validate the prediction efficiency of molecular docking simulation. The modeled ligand conformations indicated a high prediction accuracy in rigid ligand mode using cluster based analysis for most cases whereas the flexible ligand mode required further considerations such as ligand binding energy and RMSD for some cases. This in silico study is expected to serve as a platform in the screening of novel ligands against lipocalin family of proteins.