• Journal of Integrative Natural Science
• /
• 제6권3호
• /
• pp.138-142
• /
• 2013

The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

• Journal of Integrative Natural Science
• /
• 제7권2호
• /
• pp.75-78
• /
• 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.

• Journal of Integrative Natural Science
• /
• 제11권1호
• /
• pp.19-24
• /
• 2018

CRFR is involved in the pathophysiology of various disorders including depression, stress, anxiety, post-traumatic stress disorder, and addiction. The discovery of novel and structurally diverse CRF1 receptor inhibitors becomes essential. In this study, we have performed molecular docking of CRF1R with the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolines as CRF1R inhibitors. The antagonist molecules were optimized and docked into the binding site of the receptor. On analysing the docked complexes we have identified that the residues HIS214, THR215, ARG227, ARG1008, LYS1060 and ASP1061 are important in forming hydrogen bond with the inhibitors. Further studies on these residues could reveal important structural features required for the formation of CRF1R-inhibitor complex and thus in the discovery of novel and potent inhibitors.

• 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.

• Genomics & Informatics
• /
• 제12권4호
• /
• pp.283-288
• /
• 2014

Among all serious diseases globally, diabetes (type 1 and type 2) still poses a major challenge to the world population. Several target proteins have been identified, and the etiology causing diabetes has been reasonably well studied. But, there is still a gap in deciding on the choice of a drug, especially when the target is mutated. Mutations in the KCNJ11 gene, encoding the kir6.2 channel, are reported to be associated with congenital hyperinsulinism, having a major impact in causing type 1 diabetes, and due to the lack of its 3D structure, an attempt has been made to predict the structure of kir6.2, applying fold recognition methods. The current work is intended to investigate the affinity of four phytochemicals namely, curcumin (Curcuma longa), genistein (Genista tinctoria), piperine (Piper nigrum), and pterostilbene (Vitis vinifera) in a normal as well as in a mutant kir6.2 model by adopting a molecular docking methodology. The phytochemicals were docked in both wild and mutated kir6.2 models in two rounds: blind docking followed by ATP-binding pocket-specific docking. From the binding pockets, the common interacting amino acid residues participating strongly within the binding pocket were identified and compared. From the study, we conclude that these phytochemicals have strong affinity in both the normal and mutant kir6.2 model. This work would be helpful for further study of the phytochemicals above for the treatment of type 1 diabetes by targeting the kir6.2 channel.

• Journal of Advanced Navigation Technology
• /
• 제23권2호
• /
• pp.125-133
• /
• 2019

In this paper, a new study was performed on the docking of AUV to docking station using light and light sensor system under the water. For this, a guiding system for AUV loading sensor system composed of lense, light sensor, signal processor, and processor and docking system with LED are proposed. An analysis on light sensor system and light-collecting lense to obtain accurate relative angle and measurement accuracy was performed. To prove this, the system was built and a basic experiment was performed. Finally, the feasibility of the developed docking system was verified the test in the water tank.

• YAKHAK HOEJI
• /
• 제46권6호
• /
• pp.416-425
• /
• 2002

A comparative study to validate the reliability of a fully automated docking program, FlexiDock, was carried out to predict the binding modes of DHFR-inhibitor complex. The inhibitors were extracted from the crystallographically determined DHFR-NADP$^{+}$(H)-inhibitor ternary complexes of human, Escherichia coli and Candida albicans and then docked back into the remaining DHFR-NADP$^{+}$(H) binary complexes using FlexiDock. The resulting conformations and orientations were compared to the original crystal complex structures for reproducibility. Then, folate, the substrate, and known inhibitors such as methotrexate, piritrexim and trimethoprim were docked into the wild-type human DHFR and their binding modes were compared with X-ray crystallographic or other modeling data. The root mean square deviations (RMSDs) for ligands ranged from 1.14 to 1.57$\AA$, and the protein backbone RMSDs from 0.94 to 1.26$\AA$. FlexiDock reproduced the orientations and binding modes of all seven ligands in good agreement with the crystal structures. It proved to be a reliable and efficient program in studying binding modes of DHFR-inhibitor complexes of different species, and the information obtained from this work may provide additional insight into the design of new agents with improved activity.ity.

• Journal of Ocean Engineering and Technology
• /
• 제17권1호
• /
• pp.1-7
• /
• 2003

Autonomous underwater vehicles (AUVs) are unmanned, underwater vessels that are used to investigate sea environments in the study of oceanography. Docking systems are required to increase the capability of the AUVs, to recharge the batteries, and to transmit data in real time for specific underwater works, such as repented jobs at sea bed. This paper presents a visual :em control system used to dock an AUV into an underwater station. A camera mounted at the now center of the AUV is used to guide the AUV into dock. To create the visual servo control system, this paper derives an optical flow model of a camera, where the projected motions of the image plane are described with the rotational and translational velocities of the AUV. This paper combines the optical flow equation of the camera with the AUVs equation of motion, and deriver a state equation for the visual servo AUV. Further, this paper proposes a discrete-time MIMO controller, minimizing a cost function. The control inputs of the AUV are automatically generated with the projected target position on the CCD plane of the camera and with the AUVs motion. To demonstrate the effectiveness of the modeling and the control law of the visual servo AUV simulations on docking the AUV to a target station are performed with the 6-dof nonlinear equations of REMUS AUV and a CCD camera.

• Genomics & Informatics
• /
• 제12권4호
• /
• pp.276-282
• /
• 2014

The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.

• 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.