Molecular Docking Technique to Understand Enzyme-Ligand Interactions

2016 ◽  
pp. 246-266
Author(s):  
Kailas Dashrath Sonawane ◽  
Maruti Jayram Dhanavade
Keyword(s):  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Docking Studies ◽  
Atomic Level ◽  
Therapeutic Approaches ◽  
Lead Compounds ◽  
New Therapeutic Approaches ◽  
Docking Method ◽  
Ligand Interactions ◽  
Molecular Information

Molecular docking has advanced to such an extent that one can rapidly and accurately identify pharmaceutically useful lead compounds. It is being used routinely to understand molecular interactions between enzyme and ligand molecules. Several computational approaches are combined with experimental work to investigate molecular mechanisms in detail at the atomic level. Molecular docking method is also useful to investigate proper orientation and interactions between receptor and ligand. In this chapter we have discussed protein-protein approach to understand interactions between enzyme and amyloid beta (Aß) peptide. The Aß peptide is a causative agent of Alzheimer's disease. The Aß peptides can be cleaved specifically by several enzymes. Their interactions with Aß peptide and specific enzyme can be investigated using molecular docking. Thus, the molecular information obtained from docking studies might be useful to design new therapeutic approaches in treatment of Alzheimer's as well as several other diseases.

scholarly journals Molecular Docking Technique to Understand Enzyme-Ligand Interactions

2017 ◽  
pp. 727-746
Author(s):  
Kailas Dashrath Sonawane ◽  
Maruti Jayram Dhanavade
Keyword(s):  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Docking Studies ◽  
Atomic Level ◽  
Therapeutic Approaches ◽  
Lead Compounds ◽  
New Therapeutic Approaches ◽  
Docking Method ◽  
Ligand Interactions ◽  
Molecular Information

Molecular docking has advanced to such an extent that one can rapidly and accurately identify pharmaceutically useful lead compounds. It is being used routinely to understand molecular interactions between enzyme and ligand molecules. Several computational approaches are combined with experimental work to investigate molecular mechanisms in detail at the atomic level. Molecular docking method is also useful to investigate proper orientation and interactions between receptor and ligand. In this chapter we have discussed protein-protein approach to understand interactions between enzyme and amyloid beta (Aß) peptide. The Aß peptide is a causative agent of Alzheimer's disease. The Aß peptides can be cleaved specifically by several enzymes. Their interactions with Aß peptide and specific enzyme can be investigated using molecular docking. Thus, the molecular information obtained from docking studies might be useful to design new therapeutic approaches in treatment of Alzheimer's as well as several other diseases.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

Applications of Molecular Docking

2016 ◽  
pp. 278-306
Author(s):  
Josephine Anthony ◽  
Vijaya Raghavan Rangamaran ◽  
Kumar T. Shivasankarasubbiah ◽  
Dharani Gopal ◽  
Kirubagaran Ramalingam
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Fatty Acid Biosynthesis ◽  
Dynamics Simulation ◽  
Computational Techniques ◽  
Lead Compounds ◽  
Medical Interest ◽  
Insight Into

Computational tools have extended their reach into different realms of scientific research. Often coupled with molecular dynamics simulation, docking provides comprehensive insight into molecular mechanisms of biological processes. Influence of molecular docking is highly experienced in the field of structure based drug discovery, wherein docking is vital in validating novel lead compounds. The significance of molecular docking is also understood in several environmental and industrial research, in order to untangle the interactions among macromolecules of non-medical interest. Various processes such as bioremediation (REMEDIDOCK), nanomaterial interactions (NANODOCK), nutraceutical interactions (NUTRADOCK), fatty acid biosynthesis (FADOCK), and antifoulers interactions (FOULDOCK) find the application of molecular docking. This chapter emphasizes the involvement of computational techniques in the aforementioned fields to expand our knowledge on macromolecular interacting mechanisms.

scholarly journals Neuroinflammatory Nexus of Pediatric Epilepsy

2018 ◽  
Vol 07 (02) ◽  
pp. 032-039
Author(s):  
Shruti Bagla ◽  
Alan Dombkowski
Keyword(s):  
Inflammatory Mediators ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Recent Literature ◽  
Refractory Epilepsy ◽  
Genetic Mutation ◽  
Pediatric Epilepsy ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

AbstractA rapidly growing body of evidence supports the premise that neuroinflammation plays an important role in initiating and sustaining seizures in a range of pediatric epilepsies. Clinical and experimental evidence indicates that neuroinflammation is both an outcome and a contributor to seizures. In this manner, seizures that arise from an initial insult (e.g., infection, trauma, and genetic mutation) contribute to an inflammatory response that subsequently promotes recurrent seizures. This cyclic relationship between seizures and neuroinflammation has been described as a “vicious cycle.” Studies of human tissue resected for surgical treatment of refractory epilepsy have reported activated inflammatory and immune signaling pathways, while animal models have been used to demonstrate that key inflammatory mediators lead to increased seizure susceptibility. Further characterization of the molecular mechanisms involved in this cycle may ultimately enable the development of new therapeutic approaches for the treatment of epilepsy. In this brief review, we focus on key inflammatory mediators that have become prominent in recent literature of epilepsy, including newly characterized microRNAs and their potential role in neuroinflammatory signaling.

scholarly journals The structural diversity of ginsenosides affects their cholinesterase inhibitory potential

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Eda Özturan Özer ◽  
Oya Unsal Tan ◽  
Suna Turkoglu
Keyword(s):  
Molecular Docking ◽  
Enzyme Inhibitor ◽  
Direct Interaction ◽  
Structural Diversity ◽  
Docking Studies ◽  
Catalytic Triad ◽  
Active Components ◽  
Molecular Docking Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractBackground/ObjectiveGinsenosides, the major active components of the ginseng, are known to have various effects on nervous systems. The present study aimed to clarify the inhibition potentials of ginsenosides Rb1, Rc, Re and Rg1 on acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activities, and to evaluate the underlying mechanisms of inhibitions provided by protein-ligand interactions considering their probable candidates of prodrug.Materials and methodsThe inhibitory mechanisms of ginsenosides related with their structural diversity were analyzed kinetically and protein-ligand interactions for both enzymes were evaluated with most potent ginsenosides, by molecular docking studies.ResultsGinsenosides Re and Rg1, with sugar moieties attached to the C-6 and C-20 positions of core structure were found to possess the most powerful inhibitory effect on AChE and BChE activities. Molecular docking studies have been confirmed by kinetic studies. Ginsenosides having a direct interaction with amino acid residues belonging to the catalytic triad revealed the most powerful inhibition with lowest enzyme-inhibitor dissociation constant (Ki) values.ConclusionsGinsenosides Re and Rg1, either alone or in a specific combination, may provide beneficial effects on neurodegenerative pathologies in therapeutic terms.

scholarly journals Antiviral potential of phytoligands against chymotrypsin-like protease of COVID‐19 virus using molecular docking studies: An optimistic approach

2020 ◽  
Author(s):  
Ratish Chandra Mishra ◽  
Rosy Kumari ◽  
Shivani Yadav ◽  
Jaya Parkash Yadav
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Drug Repositioning ◽  
Docking Studies ◽  
The Novel ◽  
Lead Compounds ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
The City ◽  
Ucsf Chimera

Abstract A recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, Hubei province, China and its ensuing worldwide spread have resulted in lakhs of infections and thousands of deaths. As of now, there are no registered therapies for treating the contagious COVID‐19 infections, henceforth drug repositioning may provide a fast way out. In the present study, a total of thirty-five compounds including commonly used anti-viral drugs were screened against chymotrypsin-like protease (3CLpro) using SwissDock. Interaction between amino acid of targeted protein and ligands was visualized by UCSF Chimera. Docking studies revealed that the phytochemicals such as cordifolin, anisofolin A, apigenin 7-glucoside, luteolin, laballenic acid, quercetin, luteolin-4-glucoside exhibited significant binding energy with the enzyme viz. - 8.77, -8.72, -8.36, -8.35, -8.13, -8.04 and -7.87 Kcal/Mol respectively. Therefore, new lead compounds can be used for drug development against SARS‐CoV‐2 infections.

scholarly journals Anti-staphylococcal activity and mode of action of thioridazine photoproducts

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tatiana Tozar ◽  
Sofia Santos Costa ◽  
Ana-Maria Udrea ◽  
Viorel Nastasa ◽  
Isabel Couto ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Molecular Docking ◽  
Infectious Diseases ◽  
Molecular Mechanisms ◽  
Dynamic Surface Tension ◽  
Docking Studies ◽  
Gram Positive ◽  
Dynamic Surface ◽  
Gram Positive Bacteria

Abstract Antibiotic resistance became an increasing risk for population health threatening our ability to fight infectious diseases. The objective of this study was to evaluate the activity of laser irradiated thioridazine (TZ) against clinically-relevant bacteria in view to fight antibiotic resistance. TZ in ultrapure water solutions was irradiated (1–240 min) with 266 nm pulsed laser radiation. Irradiated solutions were characterized by UV–Vis and FTIR absorption spectroscopy, thin layer chromatography, laser-induced fluorescence, and dynamic surface tension measurements. Molecular docking studies were made to evaluate the molecular mechanisms of photoproducts action against Staphylococcus aureus and MRSA. More general, solutions were evaluated for their antimicrobial and efflux inhibitory activity against a panel of bacteria of clinical relevance. We observed an enhanced antimicrobial activity of TZ photoproducts against Gram-positive bacteria. This was higher than ciprofloxacin effects for methicillin- and ciprofloxacin-resistant Staphylococcus aureus. Molecular docking showed the Penicillin-binding proteins PBP3 and PBP2a inhibition by sulforidazine as a possible mechanism of action against Staphylococcus aureus and MRSA strains, respectively. Irradiated TZ reveals possible advantages in the treatment of infectious diseases produced by antibiotic-resistant Gram-positive bacteria. TZ repurposing and its photoproducts, obtained by laser irradiation, show accelerated and low-costs of development if compared to chemical synthesis.

Exploring Molecular Docking Studies of Alanine Racemase Inhibitors from Elettaria cardamomum

2019 ◽  
Vol 15 (2) ◽  
pp. 91-102
Author(s):  
Rosy Kumari ◽  
Ratish Chandra Mishra ◽  
Shivani Yadav ◽  
Jaya Parkash Yadav
Keyword(s):  
Molecular Docking ◽  
Antibacterial Agents ◽  
Docking Studies ◽  
Alanine Racemase ◽  
Heptanoic Acid ◽  
Molecular Docking Studies ◽  
Hospital Acquired Infections ◽  
Lead Compounds ◽  
Autodock 4.0 ◽  
Hospital Acquired

Background: Enterococcus faecalis has attracted much attention in recent times due to its increased virulence in hospital-acquired infections. Cardamom which is an exotic spice in food items can be proposed for its antimicrobial potential. In the present study, alanine racemase (AlaR) of the bacteria was considered as inhibitors’ target due to its crucial role in cell wall synthesis. Methods: GC-MS analysis of Cardamom extract was performed and the identified phytochemicals were docked against AlaR using AutoDock 4.0. Top score ligands were further subjected to Absorption, Distribution, Metabolism, Excretion (ADME) analysis. Results & Conclusion: Molecular docking studies reveal that among 85 phytoligands, ricinoleic acid, bombykol, 1,8- cineole, heptanoic acid, and linalool showed significant interaction to the enzyme with an energy of -7.81, -7.57, -7.03, -7.02 and -7 kcal/mol, respectively, as compared to its substrate (ΔG Alanine: -5.03 kcal/mol). Among all the five lead compounds, 1,8- cineole, heptanoic acid, and linalool exhibited high bioactivity score on druglikeliness. This enabled us to conclude that the compounds 1,8- cineole, heptanoic acid and linalool would be useful antibacterial agents against E. faecalis infections.

scholarly journals Structure Based Design and Molecular Docking Studies for Phosphorylated Tau Inhibitors in Alzheimer’s Disease

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 260 ◽  
Author(s):  
Jangampalli Pradeepkiran ◽  
P. Reddy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Toxicity Tests ◽  
Phosphorylated Tau ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Alternative Drug

The purpose of our study is to identify phosphorylated tau (p-tau) inhibitors. P-tau has recently received great interest as a potential drug target in Alzheimer’s disease (AD). The continuous failure of Aβ-targeted therapeutics recommends an alternative drug target to treat AD. There is increasing evidence and growing awareness of tau, which plays a central role in AD pathophysiology, including tangles formation, abnormal activation of phosphatases/kinases, leading p-tau aggregation in AD neurons. In the present study, we performed computational pharmacophore models, molecular docking, and simulation studies for p-tau in order to identify hyperphosphorylated sites. We found multiple serine sites that altered the R1/R2 repeats flanking sequences in the tau protein, affecting the microtubule binding ability of tau. The ligand molecules exhibited the p-O ester scaffolds with inhibitory and/or blocking actions against serine residues of p-tau. Our molecular docking results revealed five ligands that showed high docking scores and optimal protein-ligand interactions of p-tau. These five ligands showed the best pharmacokinetic and physicochemical properties, including good absorption, distribution, metabolism, and excretion (ADME) and admetSAR toxicity tests. The p-tau pharmacophore based drug discovery models provide the comprehensive and rapid drug interventions in AD, and tauopathies are expected to be the prospective future therapeutic approach in AD.

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