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Journal ArticleDOI

Molecular Docking: Approaches, Types, Applications and Basic Challenges

27 Mar 2017-Journal of analytical and bioanalytical techniques (OMICS International)-Vol. 8, Iss: 2, pp 1-3
TL;DR: Many important aspects of molecular docking in terms of its approaches, types, applications and challenges are briefly discussed in this article.
Abstract: Molecular docking is a kind of bioinformatic modelling which involves the interaction of two or more molecules to give the stable adduct. Depending upon binding properties of ligand and target, it predicts the three-dimensional structure of any complex. Molecular docking generates different possible adduct structures that are ranked and grouped together using scoring function in the software. Docking simulations predict optimized docked conformer based upon total energy of the system. In spite of all potential approaches, ligand chemistry (tautomerism and ionization), receptor flexibility (single conformation of rigid receptor) and scoring function (differentiate true binding mode) still remained the challenge. Many important aspects of molecular docking in terms of its approaches, types, applications and challenges are briefly discussed in this article.
Citations
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Journal ArticleDOI
TL;DR: Dry proniosomes could be promising stable carriers of Curcumin to be used as a safe and efficient antiviral agent and improve the therapeutic efficacy ofCurcumin.
Abstract: Curcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin. Curcumin-loaded proniosomes were fabricated by the slurry method according to 32 factorial design using Design-Expert software to demonstrate the impact of different independent variables on entrapment efficiency (EE%) and % drug released after 12 h (Q12h). The optimized formula (F5) was selected according to the desirability criteria. F5 exhibited good flowability and appeared, after reconstitution, as spherical nanovesicles with EE% of 89.94 ± 2.31% and Q12h of 70.89 ± 1.62%. F5 demonstrated higher stability and a significant enhancement of Q12h than the corresponding niosomes. The docking study investigated the ability of Curcumin to bind effectively with the active site of DNA polymerase of Herpes simplex virus (HSV). The antiviral activity and the safety of F5 were significantly higher than Curcumin. F5 improved the safety of Acyclovir (ACV) and reduced its effective dose that produced a 100% reduction of viral plaques. Proniosomes could be promising stable carriers of Curcumin to be used as a safe and efficient antiviral agent.

22 citations

Journal ArticleDOI
TL;DR: In this paper, Aspergillide B1 and 3α-hydroxy-3, 5-dihydromonacolinear L were found to be potent anti-COVID-19 drug candidates in the molecular docking study.
Abstract: AIMS: To identify the metabolites produced by the endophytic fungus, Aspergillus terreus and to explore the anti-viral activity of the identified metabolites against the pandemic disease COVID-19 in-silico METHODS AND RESULTS: Herein, we reported the isolation of A terreus, the endophytic fungus associated with soybean roots, which is then subcultured using OSMAC approach in five different culture media Analytical analysis of media ethylacetate extracts using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was carried out Furthermore, the obtained LC-MS data were statistically processed with MetaboAnalyst 40 Molecular docking studies were performed for the dereplicated metabolites against COVID-19 main protease (Mpro ) Metabolomic profiling revealed the presence of 18 compounds belonging to different chemical classes Quinones, polyketides and isocoumarins were the most abundant classes Multivariate analysis revealed that potato dextrose broth and modified potato dextrose broth are the optimal media for metabolites production Molecular docking studies declared that the metabolites, Aspergillide B1 and 3a-Hydroxy-3, 5-dihydromonacolin L showed the highest binding energy scores towards COVID-19 main protease (Mpro ) (-9·473) and (-9·386), respectively, and they interact strongly with the catalytic dyad (His41 and Cys145) amino acid residues of Mpro CONCLUSIONS: A combination of metabolomics and in-silico approaches have allowed a shorter route to search for anti-COVID-19 natural products in a shorter time The dereplicated metabolites, aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L were found to be potent anti-COVID-19 drug candidates in the molecular docking study SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the endophytic fungus, A terreus can be considered as a potential source of natural bioactive products In addition to, the possibility of developing the metabolites, aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L to be used as phytopharmaceuticals for the management of COVID-19

20 citations

Journal ArticleDOI
TL;DR: All virtual simulations corroborated with experimental results, and LQM334 could be used as a promising anti-CHIKV scaffold for designing new drugs in the future.
Abstract: Chikungunya virus (CHIKV) causes an infectious disease characterized by inflammation and pain of the musculoskeletal tissues accompanied by swelling in the joints and cartilage damage. Currently, there are no licensed vaccines or chemotherapeutic agents to prevent or treat CHIKV infections. In this context, our research aimed to explore the potential in vitro anti-CHIKV activity of acrylamide derivatives. In silico methods were applied to 132 Michael's acceptors toward the six most important biological targets from CHIKV. Subsequently, the ten most promising acrylamides were selected and synthesized. From the cytotoxicity MTT assay, we verified that LQM330, 334, and 336 demonstrate high cell viability at 40 µM. Moreover, these derivatives exhibited anti-CHIKV activities, highlighting the compound LQM334 which exhibited an inhibition value of 81%. Thus, docking simulations were performed to suggest a potential CHIKV-target for LQM334. It was observed that the LQM334 has a high affinity towards the E3-E2-E1 glycoproteins complex. Moreover, LQM334 reduced the percentage of CHIKV-positive cells from 74.07 to 0.88%, 48h post-treatment on intracellular flow cytometry staining. In conclusion, all virtual simulations corroborated with experimental results, and LQM334 could be used as a promising anti-CHIKV scaffold for designing new drugs in the future.

18 citations

Journal ArticleDOI
TL;DR: The recent shift towards highly selective and specific HSP inhibition has shown great promise as evidenced by the development of paralog/isoform-selective HSP drugs and this article further describes promising computational paradigms and their applications towards the discovery of highly specific inhibitors of oncogenic HSPs.
Abstract: Introduction: Over the years, not a single HSP inhibitor has progressed into the post-market phase of drug development despite the success recorded in various pre-clinical and clinical studies. The...

15 citations

Journal ArticleDOI
TL;DR: In this paper, the aerial parts of 32 Helichrysum species were extracted using polar (methanol:water (1:1)) and non-polar (hexane, dichloromethane and acetone) solvent systems.

15 citations

References
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Journal ArticleDOI
TL;DR: An interface between the popular molecular graphics system PyMOL and the molecular docking suites Autodock and Vina is presented and it is demonstrated how the combination of docking and visualization can aid structure-based drug design efforts.
Abstract: Docking of small molecule compounds into the binding site of a receptor and estimating the binding affinity of the complex is an important part of the structure-based drug design process. For a thorough understanding of the structural principles that determine the strength of a protein/ligand complex both, an accurate and fast docking protocol and the ability to visualize binding geometries and interactions are mandatory. Here we present an interface between the popular molecular graphics system PyMOL and the molecular docking suites Autodock and Vina and demonstrate how the combination of docking and visualization can aid structure-based drug design efforts.

1,292 citations


"Molecular Docking: Approaches, Type..." refers methods in this paper

  • ...This can be made possible using scoring function of software [4]....

    [...]

Journal ArticleDOI
TL;DR: The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.
Abstract: Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

1,120 citations


"Molecular Docking: Approaches, Type..." refers background in this paper

  • ...Docking in combination with scoring function can be used to evaluate large databases for finding out potent drug candidate in silico, which can target the molecule of interest [8]....

    [...]

Journal ArticleDOI
TL;DR: Here it is shown that using multiple fixed receptor conformations, either experimentally determined by crystallography or NMR, or computationally generated, is a practical shortcut that may improve docking calculations.

474 citations

Journal ArticleDOI
TL;DR: As the structures of more and more proteins and nucleic acids become available, molecular docking is increasingly considered for lead discovery and the 'drug-likeness' and specificity of docking hits is also being examined.

433 citations


"Molecular Docking: Approaches, Type..." refers background or methods in this paper

  • ...This can be used to develop more potent, selective and efficient drug candidates [5,7]....

    [...]

  • ...To overcome this problem, different scoring functions are employed such as consensus scoring; appliance of number of score functions to the same docked pose in order to eliminate false positives [5]....

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  • ...This approach is rather quick and involves the rapid scanning of numerous thousands of ligands in a few seconds to find out the possible binding properties of ligand on target molecular surface [5,6]....

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Journal ArticleDOI
TL;DR: The main topics and recent computational and methodological advances in protein–ligand docking are summarised, including protein flexibility, multiple ligand binding modes and the free-energy landscape profile for binding affinity prediction.
Abstract: Docking methodology aims to predict the experimental binding modes and affinities of small molecules within the binding site of particular receptor targets and is currently used as a standard computational tool in drug design for lead compound optimisation and in virtual screening studies to find novel biologically active molecules. The basic tools of a docking methodology include a search algorithm and an energy scoring function for generating and evaluating ligand poses. In this review, we present the search algorithms and scoring functions most commonly used in current molecular docking methods that focus on protein–ligand applications. We summarise the main topics and recent computational and methodological advances in protein–ligand docking. Protein flexibility, multiple ligand binding modes and the free-energy landscape profile for binding affinity prediction are important and interconnected challenges to be overcome by further methodological developments in the docking field.

301 citations


"Molecular Docking: Approaches, Type..." refers background in this paper

  • ...Molecular docking is an attractive scaffold to understand drugbiomolecular interactions for the rational drug design and discovery, as well as in the mechanistic study by placing a molecule (ligand) into the preferred binding site of the target specific region of the DNA/protein (receptor) mainly in a non-covalent fashion to form a stable complex of potential efficacy and more specificity [1,2]....

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