Comparing protein–ligand docking programs is difficult

Cole, Jason C.; Murray, Christopher W.; Nissink, J. Willem M.; Taylor, Richard D.; Taylor, Robin

doi:10.1002/prot.20497

Cited by 305 publications

(294 citation statements)

References 43 publications

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“…In line with the two main tasks carried out by docking programs, evaluation thereof normally revolves about pose prediction and affinity prediction. As also noted by others, comparison and assessment of docking programs are not easy tasks [119]. Quite a number of studies comparing docking programs and assessing their performance have been published [6,23,89,[120][121][122][123][124][125][126][127][128].…”

Section: Assessment Of Docking Performancementioning

confidence: 99%

Structure-Based Drug Design: Docking and Scoring

Kroemer

2007

CPPS

272

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This review gives an introduction into ligand -receptor docking and illustrates the basic underlying concepts. An overview of different approaches and algorithms is provided. Although the application of docking and scoring has led to some remarkable successes, there are still some major challenges ahead, which are outlined here as well. Approaches to address some of these challenges and the latest developments in the area are presented. Some aspects of the assessment of docking program performance are discussed. A number of successful applications of structure-based virtual screening are described.

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Section: Assessment Of Docking Performancementioning

confidence: 99%

Structure-Based Drug Design: Docking and Scoring

Kroemer

2007

CPPS

272

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“…given the uncertainty from protein superposition and the fact that the binding mode can be properly conveyed even for RMSD values above 2.0 Å [43,44], a threshold of 2.5 Å is reasonable for recognizing correctly docked structures. In our study, we retain the definition of 2.5 Å as our evaluation threshold.…”

Section: Docking Protocol and Cross-dockingmentioning

confidence: 99%

Insight into ligand selectivity in HCV NS5B polymerase: molecular dynamics simulations, free energy decomposition and docking

Froeyen

Herdewijn

2009

J Mol Model

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Modeling studies were performed on HCV NS5B Polymerase in an effort to design new inhibitors. The binding models of five different scaffold inhibitors were investigated and compared by using molecular dynamics simulations, free energy calculation and decomposition. Our results show Tyr448 plays the most critical role in the binding of most inhibitors. In addition, favorable contributions of residues Pro197, Arg200, Cys366, Met414 and Tyr448 in a deep hydrophobic pocket prove to be important for the selectivity of inhibitors. Furthermore, an optimized docking protocol was presented based on cross-docking the five inhibitors in the palm binding site of this enzyme using the Autodock program. This protocol was used later to virtually screen NCI and Maybridge diversity set libraries. The binding site was profiled via the statistics and analysis of the hydrogen bond networks formed between the receptor and the top-ranked diversity set compounds. Based on our detailed binding site analysis two useful rules were proposed to guide the selection of promising hits.Response to Reviewers: Question1: It is a pity that nothing in detail is discussed about found structures resulting from the virtual screening. Did the authors find new promising ligands with high (higher than the template ligands?) affinity and are they structurally diverse or similar to the used ones?Answer: We have found some promising compounds after the virtual screening. They are structurally diverse. Most of them form hydrogen bonds with the critical residues such as Tyr448 and have strong hydrophobic interaction with the residues in the deep hydrophobic pocket mentioned in our article. These compounds are under biological test.Question2: Additionally to figure 5 at least one figure should be added, showing the amino acid residues of the active site with the discussed most important interactions with one (the best?) ligand. This would considerably help to understand the discussion without looking in the original pdb-files. AbstractModeling studies were performed on HCV NS5B Polymerase in an effort to design new inhibitors. The binding models of five different scaffold inhibitors were investigated and compared by using molecular dynamics simulations, free energy calculation and decomposition. Our results show Tyr448 plays the most critical role in the binding of most inhibitors. In addition, favorable contributions of residues Pro197, Arg200, Cys366, Met414 and Tyr448 in a deep hydrophobic pocket prove to be important for the selectivity of inhibitors.Furthermore, an optimized docking protocol was presented based on cross-docking the five inhibitors in the palm binding site of this enzyme using the Autodock program. This protocol was used later to virtually screen NCI and Maybridge diversity set libraries. The binding site was profiled via the statistics and analysis of the hydrogen bond networks formed between the receptor and the top-ranked diversity set compounds. Based on our detailed binding site analysis two useful rules were proposed to ...

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“…Serum marker such as serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) were measured (Cole et al, 2005;Silverstein and Webster, 1963). Lipid profile like triglyceride and total cholesterol were also measured using test kits.…”

Section: Biochemical Estimationmentioning

confidence: 99%

Design, synthesis and anti-diabetic activity of some novel xanthone derivatives targeting α-glucosidase

Bairy

Das

Nainwal

et al. 2016

Bangladesh J Pharmacol

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Twenty eight xanthone derivatives were designed and docked into the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM) by considering Miglitol as standard drug. Most of the molecules showed excellent docking scores and docking interaction as compared to the binding cavity of the standard molecule. The five best scoring ligands were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were screened for the in vivo antidiabetic activity in streptozotocin (STZ) induced diabetic animal model in Wistar rats. Compound P4 showed the most prominent inhibition among others. The synthesized compounds reported significant (p< 0.01) effect of lowering glucose levels in the blood compared to miglitol as a standard α-glucosidase inhibitor.Video clipInduction of diabetes:

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Comparing protein–ligand docking programs is difficult

Cited by 305 publications

References 43 publications

Structure-Based Drug Design: Docking and Scoring

Structure-Based Drug Design: Docking and Scoring

Insight into ligand selectivity in HCV NS5B polymerase: molecular dynamics simulations, free energy decomposition and docking

Design, synthesis and anti-diabetic activity of some novel xanthone derivatives targeting α-glucosidase

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