• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.221-233
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• 2004

Molecular docking falls into the general category of global optimization problems since its main purpose is to find the most stable complex consisting of a receptor and its ligand. Conformational space annealing (CSA), a powerful global optimization method, is incorporated with the Tinker molecular modeling package to perform molecular docking simulations of six receptor-ligand complexes (3PTB, 1ULB, 2CPP, 1STP, 3CPA and 1PPH) from the Protein Data Bank. In parallel, Monte Carlo with minimization (MCM) method is also incorporated into the Tinker package for comparison. The energy function, consisting of electrostatic interactions, van der Waals interactions and torsional energy terms, is calculated using the AMBER94 all-atom empirical force field. Rigid docking simulations for all six complexes and flexible docking simulations for three complexes (1STP, 3CPA and 1PPH) are carried out using the CSA and the MCM methods. The simulation results show that the docking procedures using the CSA method generally find the most stable complexes as well as the native -like complexes more efficiently and accurately than those using the MCM, demonstrating that CSA is a promising search method for molecular docking problems.

• The Journal of the Korea Contents Association
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• v.8 no.12
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• pp.441-448
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• 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.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.179-186
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• 2022

The c-Jun N-terminal kinase (JNK3) play major role in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, cerebral ischemia and other Central Nervous System disorders. Since JNK3 is primarily stated in the brain and stimulated by stress-stimuli, this situation is conceivable that inhibiting JNK3 could be a possible treatment for the mechanisms underlying neurodegenerative diseases. In this study drugs from Zinc15 database were screened to identify the JNK3 inhibitors by Molecular docking and Density functional theory approach. Molecular docking was done by Autodock vina and the ligands were selected based on the binding affinity. Our results identified top ten novel ligands as potential inhibitors against JNK3. Molecular docking revealed that Venetoclax, Fosaprepitant and Avapritinib exhibited better binding affinity and interacting with proposed binding site residues of JNK3. Density functional theory was used to compute the values for energy gap, lowest unoccupied molecular orbital (LUMO), and highest occupied molecular orbital (HOMO). The results of Density functional theory study showed that Venetoclax, Fosaprepitant and Avapritinib serves as a lead compound for the development of JNK3 small molecule inhibitors.

• Journal of Integrative Natural Science
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• v.10 no.3
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• pp.137-140
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• 2017

Diabetes mellitus has become a major growing public health problem worldwide. More than 90% of all diabetes cases are classified as type 2 diabetes (T2D), which is also known as non-insulin dependent diabetes. Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin signal transduction pathway and has emerged as novel therapeutic strategy for the treatment of type 2 diabetes. PTP1B inhibitors enhance the sensibility of insulin receptor (IR) and have favorable curing effect for insulin resistance-related diseases. Recently twelve anti-diabetic xanthones were isolated from the bark of Garcinia xanthochymus. Hence, in the present study, molecular docking was carried out for these twelve xanthones. The objective of this work is to study the interaction of the newly isolated xanthones with PTP1B. The docking results showed that xanthones have good interactions and has better docking score with PTP1B and suggest LYS120 and ASP181 are the important residues involved in interaction between PTP1B enzyme and the xanthones.

• Journal of Integrative Natural Science
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• v.9 no.1
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• pp.23-27
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• 2016

Hepatitis B virus is the leading source of liver disorders and is a global health problem and needs advancements in its treatment against increasing problems. Recently five vanitaracin derivatives were isolated from the fungus Talaromyces species which have anti-Hepatitis B virus activity. Hence, in the present study, molecular docking was carried out with five vanitaracin derivatives isolated from Talaromyces species and three known inhibitors.The objective of this work is to study the interaction of newly isolated compounds and compare its interaction with known inhibitors. The docking results revealed that vanitaracin derivatives have good interactions and has better docking score with the Hepatitis B virus and suggest SER2, SER4 and ASP30 are important residues involved in interaction with the inhibitors. These result authenticates vanitaracin derivatives contributes to inhibitory activity of Hepatitis B virus to treat liver disorders.

• Journal of Integrative Natural Science
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• v.11 no.1
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• pp.25-29
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• 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.

• Journal of Integrative Natural Science
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• v.3 no.3
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• pp.143-147
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• 2010

Since it is of great importance to know how a ligand binds to a receptor, there have been a lot of efforts to improve the quality of prediction of docking poses. Earlier efforts were focused on improving search algorithm and scoring function in a docking program resulting in a partial improvement with a lot of variations. Although these are basically very important and essential, more tangible improvements came from the reduction of search space. In a normal docking study, the approximate active site is assumed to be known. After defining active site, scoring functions and search algorithms are used to locate the expected binding pose within this search space. A good search algorithm will sample wisely toward the correct binding pose. By careful study of receptor structure, it was possible to prioritize sub-space in the active site using "receptor-based pharmacophores" or "hot spots". In a sense, these techniques reduce the search space from the beginning. Further improvements were made when the bound ligand structure is available, i.e., the searching could be directed by molecular similarity using ligand information. This could be very helpful to increase the accuracy of binding pose. In addition, if the biological activity data is available, docking program could be improved to the level of being useful in affinity prediction for a series of congeneric ligands. Since the number of co-crystal structures is increasing in protein databank, "Ligand-Guided Docking" to reduce the search space would be more important to improve the accuracy of docking pose prediction and the efficiency of virtual screening. Further improvements in this area would be useful to produce more reliable docking programs.

• Journal of Integrative Natural Science
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• v.7 no.2
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• pp.75-78
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• 2014

Computer-aided drug design uses computational chemistry to discover, enhance, or study drugs and related biologically active molecules. It is now proved to be effective in reducing costs and speeding up drug discovery. In this short review, we discussed on the importance of combining molecular docking and molecular dynamics simulation methodologies. We also reviewed the importance of protein flexibility, refinement of docked complexes using molecular dynamics and the use of free energy calculations for the calculation of accurate binding energies has been reviewed.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1479-1484
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• 2008

Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

• Natural Product Sciences
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• v.28 no.2
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• pp.45-52
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• 2022

The identification of Plasmodium falciparum enoyl acyl-carrier protein reductase (pfENR) is considered as a potential biological target against malaria. Trema orientalis is considered a rich source of phytochemicals useful in malaria treatment. This study evaluated the in-vitro inhibitory activity of the extract and isolated compounds of T. orientalis leaf; the isolated compounds and the analogues of the most active compound were subjected to in-silico molecular docking studies on pfENR. The methanolic extract of T. orientalis was subjected to repeated chromatographic separation which led to the isolation of some compounds. The isolated compounds from the plant were examined for their antimalarial activity using β-hematin inhibition assay. Virtual screening via molecular docking and ADMET studies were conducted to gain insight into the mechanism of binding of ligand and to identify effective pfENR inhibitors. The isolated compounds and the analogues of the most active isolates were gotten from PubChem library for use in docking study. Hexacosanol and β-sitosterol showed inhibition of the β-hematin formation. The docking results showed that hexacosanol, β-sitosterol and the analogues of β-sitosterol displayed binding energy ranging between -6.1 kcal/mol and -11.6 kcal/mol. Sitosterol glucoside has the highest docking score. Some of the ligands showed more binding affinity than known bioactive compounds used as reference. Analogues of β-sitosterol has been shown to be potential inhibitors of pfENR, therefore, the findings from this study suggest that sitosterol glucoside and ergosterol peroxide could act as antimalarial agents after further lead optimisation investigations.