ArgusLab Software Research Articles

In-Silico screening of Pleconaril and its novel substituted derivatives with Neuraminidase of H1N1 Influenza strain

BackgroundNeuraminidase (NA) is a prominent surface antigen of Influenza viruses, which helps in release of viruses from the host cells after replication. Anti influenza drugs such as Oseltamivir target a highly conserved active site of NA, which comprises of 8 functional residues (R118, D151, R152, R224, E276, R292, R371 and Y406) to restrict viral release from host cells, thus inhibiting its ability to cleave sialic acid residues on the cell membrane. Reports on the emergence of Oseltamivir resistant strains of H1N1 Influenza virus necessitated a search for alternative drug candidates. Pleconaril is a novel antiviral drug being developed by Schering-Plough to treat Picornaviridae infections, and is in its late clinical trials stage. Since, Pleconaril was designed to bind the highly conserved hydrophobic binding site on VP1 protein of Picorna viruses, the ability of Pleconaril and its novel substituted derivatives to bind highly conserved hydrophobic active site of H1N1 Neuraminidase, targeting which oseltamivir has been designed was investigated.Result310 novel substituted variants of Pleconaril were designed using Chemsketch software and docked into the highly conserved active site of NA using arguslab software. 198 out of 310 Pleconaril variants analyzed for docking with NA active site were proven effective, based on their free binding energy.ConclusionPleconaril variants with F, Cl, Br, CH3, OH and aromatic ring substitutions were shown to be effective alternatives to Oseltamivir as anti influenza drugs.

Potential of mangrove derived compounds against dihydrofolate reductase: An in-silico docking study

Approximately 3 billion people, one half of the world’s population, live in at-risk regions for malaria infection leading to about 250 million malaria cases every year and nearly one million deaths. Once the malarial parasite Plasmodium vivax and Plasmodium falciparum enters the red blood cells its growth is inhibited by Proguanil, a prophylactic antimalarial drug which inhibits the enzyme, dihydrofolate reductase leading to the inhibition of the growth of malarial parasites. Considering the side effects of the antimalarial drugs, the present study was undertaken to substantiate the inhibition potential of mangrove-derived compounds against the receptor protein dihydrofolate reductase. Docking studies by using Argus lab software revealed that among nine mangrove-derived compounds five compounds namely stigmasterol, triterpenoid, tretinoin, pyrethrin and rubrolide-N showed good docking energy score of -14.2239, 12.4725, -11.689, -11.1828 and -10.884 Kcal/mol, respectively against dihydrofolate reductase. Key words: Malaria, dihydrofolate reductase, mangrove-derived compounds, Pdb, Argus lab.

In silico study of the binding parameters of various antioxidants with human Paraoxonase 1

Paraoxonases are a group of enzymes involved in the hydrolysis of organophosphates. Human Paraoxonase 1 is synthesized in liver and secreted into blood, where it is associated exclusively with High Density Lipoproteins and may protect against the development of atherosclerosis. Paraoxonase was identified as a genetic risk factor for cardiovascular disease. An enhancement of Paraoxonase 1 activity by well-known anti oxidant flavonols like Quercetin and its derivatives are therefore of interest. The aim of this study is to investigate the binding parameters of Quercetin and its derivatives such as Quercetin dihydrate, Quercetin pentaacetate and Quercetin -3-methylether with Paraoxonase. Human Paraoxonase 1 was modeled using Modeller and binding parameters were studied using Arguslab software. The interactions show the differences in their binding and will throw light on new ways of effecting High Density Lipoprotein content and action. The docking studies helped in understanding the binding parameters thereby giving a direction for future anti-atherosclerotic treatment options. Key words: Paraoxonases, quercetin, anti-oxidant, high density lipoproteins (HDL), atherosclerosis.

Structural Study on the Complex of Ortho-Ester Tetra Azophenylcalix[4]arene (TEAC) with Th(IV)

A new 1:1 complex between Ortho-Ester Tetra-Azophenylcalix[4]arene (TEAC) and Thorium(IV) was found in weakly acidic medium (pH =4-5), ?max = 520 nm, Beer’s law was obeyed in the range 2.5 ×10-6 – 2.5×10-5 mol.L-1 of Th(IV), the limit of detection was 1.0 × 10? 6 mol.L-1 and linear regression equation was determined to be: absorbance (A) = 0,248×C(10-5 mol.L-1) + 0,02 (R2 = 0,990, n =7). The FT-IR, HNMR, Raman spectroscopies were also used to provide the existence of this complex, and the Molecular Mechanics (MM) method in Arguslab software was applied to optimize the structure. The energy of the system, QEq charge, bond lengths and bond angles were also calculated by this program. Combining all data, the structure of complex TEAC - Th(IV) has been proposed.

Molecular docking study of bark-derived components of Cinnamomum cassia on aldose reductase

Aldose reductase (AR) is an enzyme associated with retinopathy of both type 1 and type 2 diabetic patients. AR is inhibited by giving chemical drugs to prevent diabetic retinopathy, but is associated with deleterious side effects. Compounds isolated from plants are safer than chemical drugs and have a lot of potential. In the present study, three components viz., cinnamaldehyde, cinnamic acid and cinnamyl alcohol derived from the bark of Cinnamomum cassia were used to evaluate their efficiency in inhibiting AR activity. For this, the AR protein structure database was downloaded from PDB and its pictorial database was downloaded from PDBsum. Structural visualization of AR was done by RasMol. Using Q-SiteFinder, prediction of ligand binding site was done. The three dimensional structures of inhibitors viz., cinnamaldehyde, cinnamic acid and cinnamyl alcohol were downloaded from ChemSketch. Docking studies were carried out using ArgusLab software. Docking studies of cinnamaldehyde, cinnamic acid and cinnamyl alcohol against AR was undertaken to gain insight into the binding mode of the investigated compounds at the active site of AR. All compounds were found to be active against AR as indicated by docking results; the best being cinnamaldehyde. Results suggest that cinnamaldehyde, cinnamic acid and cinnamyl alcohol should be evaluated further for therapeutic use in combination with other diabetic drugs. Further, this may be confirmed by drug trials in animal models to find out the optimum dose and its efficiency in inhibiting AR activity to treat diabetic related complications. Keywords: Diabetes, aldose reductase, cinnamon, molecular docking.

Molecular docking study of bark-derived components of Cinnamomum cassia on aldose reductase

Aldose reductase (AR) is an enzyme associated with retinopathy of both type 1 and type 2 diabetic patients. AR is inhibited by giving chemical drugs to prevent diabetic retinopathy, but is associated with deleterious side effects. Compounds isolated from plants are safer than chemical drugs and have a lot of potential. In the present study, three components viz ., cinnamaldehyde, cinnamic acid and cinnamyl alcohol derived from the bark of Cinnamomum cassia were used to evaluate their efficiency in inhibiting AR activity. For this, the AR protein structure database was downloaded from PDB and its pictorial database was downloaded from PDBsum. Structural visualization of AR was done by RasMol. Using Q-SiteFinder, prediction of ligand binding site was done. The three dimensional structures of inhibitors viz ., cinnamaldehyde, cinnamic acid and cinnamyl alcohol were downloaded from ChemSketch. Docking studies were carried out using ArgusLab software. Docking studies of cinnamaldehyde, cinnamic acid and cinnamyl alcohol against AR was undertaken to gain insight into the binding mode of the investigated compounds at the active site of AR. All compounds were found to be active against AR as indicated by docking results; the best being cinnamaldehyde. Results suggest that cinnamaldehyde, cinnamic acid and cinnamyl alcohol should be evaluated further for therapeutic use in combination with other diabetic drugs. Further, this may be confirmed by drug trials in animal models to find out the optimum dose and its efficiency in inhibiting AR activity to treat diabetic related complications

Molecular Docking Studies of Antimalarial Drugs for Malaria

Malaria is the most important parasitic disease in humans, with transmission occurring in over 100 countries with a population of three billion people. It is caused by protozoan parasites of the genus Plasmodium. These parasites are transmitted from one person to another by the female anopheles mosquito. Proguanil is a prophylactic antimalarial drug, it stops the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase. The side effects of these drugs make the need for the necessity of new improved drugs Conformational analysis and geometry optimization of Proguanil was performed using Argus Lab & Hex software. When the receptor (DHFR) was docked with the drug Proguanil the energy value obtained was (-6.59) using Argus Lab and (-174.54) using hex. The most feasible position for the drug to interact with the receptor was found to be with analog 2 having energy -9.56 K.cal/mole using Argus Lab and -201.92 K.cal/mole using HEX Tool. So Proguanil Analog 2 sketched using Chemsketch is detected with more signifi cant energy values in both softwares and probable lead molecules. Further from ADME/T properties of the Analogs is also showing the better result than available drug.

Evaluation of Docking Accuracy and Investigations of Roles of Parameters and Each Term in Scoring Functions for Protein–Ligand Docking Using ArgusLab Software

Abstract We evaluated the docking accuracy of ArgusLab, which is a freely available software program for computational docking, using experimentally determined protein–ligand complex structures. Investigations of the roles of parameters used for docking calculations in ArgusLab were carried out in addition to evaluation of the software. The results indicate that one docking engine of ArgusLab, GADock, is superior in terms of accuracy, and that another docking engine, ArgusDock, is advantageous in terms of the computational time it provides. In a pose construction step, larger population sizes generated more accurate poses using GADock. The docking poses constructed by GADock were easier to evaluate than those of ArgusDock in the pose-selection step. Reliable docking calculations are expected to be carried out with ArgusLab using results of this study.