Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery

Meng, Xuan-Yu; Zhang, Hongxing; Mezei, Mihaly; Cui, Meng

doi:10.2174/157340911795677602

Cited by 2,175 publications

(1,145 citation statements)

References 137 publications

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“…This drug virtual-screening method is widely applied in structurebased drug design and can be performed for interaction modelling of ligands and proteins at an atomic level [21]. The chemical structure of certain drug receptor is downloaded from the Protein Data Bank (PDB) for investigation of their molecular docking capability at the active site, using computer algorithms and scoring functions [22].…”

Section: Introductionmentioning

confidence: 99%

“…The chemical structure of certain drug receptor is downloaded from the Protein Data Bank (PDB) for investigation of their molecular docking capability at the active site, using computer algorithms and scoring functions [22]. This consists of basic processes, namely ligand conformation predictions at the receptor active site, placement and orientation of the conformations, and their binding affinity [21]. Interactions between ligands and receptors, as indicated by their scoring function, are ranked; ligands with the lowest score will be investigated further.…”

Section: Introductionmentioning

confidence: 99%

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In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Miladiyah

Jumina

Haryana

et al. 2017

Int J Pharm Pharm Sci

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Objective: To demonstrate the potential ofdifferent xanthone derivatives as cyclooxygenase-2 (COX-2) inhibitor agents and their selectivity against cycloooxygenase-1 (COX-1) and COX-2 using molecular simulation. Methods:Nine novel xanthone derivatives (compounds A-I) were employed to dock against protein COX-2 (Protein Data Bank/PDB ID: 1CX2) and COX-1 (PDB ID: 3N8Z). Celecoxib, a selective COX-2 inhibitor, was chosen as a control compound. The free binding energy produced by the docking was scored using Protein-Ligand Ant System (PLANTS) and the hydrogen bonds (H-bonds) between ligands and enzymes were visualised using Pymol.Results: Molecular docking studies revealed that celecoxib docked to the active site of COX-2 enzyme, but not to COX-1; where as xanthone derivatives docked to the active site of both COX-2 and COX-1. Free binding energy of xanthone derivatives ranged between-73, 57 to-79,18 and between-73,06 to-79,25 against COX-2 and COX-1, respectively, and-78,13 against celecoxib. H-bonds in the molecule of xanthone derivatives and COX-2 protein were found in amino acid residues Arg 120 , Tyr 355 , Tyr 385 , and Ser 353 . There was an insignificant difference between the free binding energyof xanthone derivatives against COX-2 and against COX-1, suggesting that their inhibition was non-selective. Conclusion:In conclusion, in silico studies showed that xanthone derivatives could be effective as potential inhibitors against COX-2, although they are not selective.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Miladiyah

Jumina

Haryana

et al. 2017

Int J Pharm Pharm Sci

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“…The presence of experimentally determined structure of target molecule would allow following the second type of methodology. This includes the molecular docking (MD) [20], QM-Polarized Ligand Dicking (QPLD) [21] or/and the three-dimensional quantitative-structure activity relationships (3D QSAR) [22,23].…”

Section: Introductionmentioning

confidence: 99%

Geometry optimization of steroid sulfatase inhibitors - the influence on the free binding energy with STS

et al. 2017

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In the paper we review the application of two techniques (molecular mechanics and quantum mechanics) to study the influence of geometry optimization of the steroid sulfatase inhibitors on the values of descriptors coded their chemical structure and their free binding energy with the STS protein. We selected 22 STS-inhibitors and compared their structures optimized with MM+, PM7 and DFT B3LYP/6-31++G* approaches considering separately the bond lengths, angles, dihedral angles and total energies. We proved that different minimum energy conformers could be generated depending on the choice of the optimization method. However, the results indicated that selection of the geometry optimization method did not affect the optimal STS inhibitor coordinates, and hence the values of molecular descriptors which describe the 3D structure of the molecule. To study the interaction pattern of the STS inhibitors (optimized using different methods) with the target receptor we applied two strategies: AutoDock and PathDock. The docking studies point out that selection of software to docking simulation is one of the crucial factors determining the binding mode of STS inhibitors with their molecular target. Other factor is related to the ligand orientation in the binding pocket. Finally, obtained results indicate that MM+ and PM7 methods (faster and less expensive) could be successfully employed to geometry optimization of the STS inhibitors before their docking procedure as well as for molecular descriptors calculations.

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“…Molecular docking studies were also carried out to understand the binding pattern and to support in vitro antimicrobial data of synthesized most active compound [27,28]. Automated docking technique was used to determine the orientation of inhibitors, bound in the active site of β-ketoacyl-acyl carrier protein synthase III (FabH; pdb id:3IL7) [29].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Modeling, and Quantitative Structure–activity Relationship Studies of Undec-10-Enehydrazide Derivatives as Antimicrobial Agents

Kumari

Narang

Nayak

et al. 2017

Asian J Pharm Clin Res

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Objective: In recent years, an increasing frequency and severity of antimicrobial resistance to different antimicrobial agents, demands new remedies for the treatment of infections. Therefore, in this study, a series of undec-10-enehydrazide derivatives were synthesized and screened for in vitro activity against selected pathogenic microbial strains. Methods:The synthesis of the intermediate and target compounds was performed by standard procedure. Synthesized compounds were screened for antimicrobial activity by tube dilution method. Molecular docking study of synthesized derivatives was also performed to find out their interaction with the target site of β-ketoacyl-acyl carrier protein synthase III, (FabH; pdb id:3IL7) by docking technique. Quantitative structure-activity relationship (QSAR) studies were also performed to correlate antimicrobial activity with structural properties of synthesized molecules.Results: Antimicrobial screening results showed that compound 8 having benzylidine moiety with methoxy groups at meta and para position and compound 16 having 3-chloro-2-(3-flourophenyl)-4-oxoazetidine moiety was found to be most potent. QSAR studies revealed the importance of Randic topology parameter (R) in describing the antimicrobial activity of synthesized derivatives. Molecular docking study indicated hydrophobic interaction of deeply inserted aliphatic side chain of the ligand with FabH. The N-atoms of hydrazide moiety interacts with Ala246 and Asn247 through H-bonding. The m-and p-methoxy groups form H-bond with water and side chain of Arg36, respectively. Conclusion:Compound 8 having benzylidine moiety with methoxy groups at meta and para position and compound 16 having 3-chloro-2-(3-flourophenyl)-4-oxoazetidine moiety was found to most potent antibacterial and antifungal compounds, respectively.

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Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery

Cited by 2,175 publications

References 137 publications

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Geometry optimization of steroid sulfatase inhibitors - the influence on the free binding energy with STS

Synthesis, Molecular Modeling, and Quantitative Structure–activity Relationship Studies of Undec-10-Enehydrazide Derivatives as Antimicrobial Agents

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