Prediction of Protein–Ligand Binding Poses via a Combination of Induced Fit Docking and Metadynamics Simulations

2016 ◽  
Vol 12 (6) ◽  
pp. 2990-2998 ◽  
Author(s):  
Anthony J. Clark ◽  
Pratyush Tiwary ◽  
Ken Borrelli ◽  
Shulu Feng ◽  
Edward B. Miller ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Induced Fit Docking ◽  
Induced Fit

A Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding

2020 ◽  
Author(s):  
Edward Miller ◽  
Robert Murphy ◽  
Daniel Sindhikara ◽  
Ken Borrelli ◽  
Matthew Grisewood ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Structure Prediction ◽  
Heavy Atom ◽  
Accurate Solution ◽  
Binding Modes ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Test Set ◽  
Cross Docking ◽  
Public Data

We present a reliable and accurate solution to the induced fit docking problem for protein-ligand binding by combining ligand-based pharmacophore docking (Phase), rigid receptor docking (Glide), and protein structure prediction (Prime) with explicit solvent molecular dynamics simulations. We provide an in-depth description of our novel methodology and present results for 41 targets consisting of 415 cross-docking cases divided amongst a training and test set. For both the training and test-set, we compute binding modes with a ligand-heavy atom RMSD to within 2.5 Å or better in over 90% of cross-docking cases compared to less than 70% of cross-docking cases using our previously published induced-fit docking algorithm and less than 41% using rigid receptor docking. Applications of the predicted ligand-receptor structure in free energy perturbation calculations is demonstrated for both public data and in active drug discovery projects, both retrospectively and prospectively.

A Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding

2020 ◽  
Author(s):  
Edward Miller ◽  
Robert Murphy ◽  
Daniel Sindhikara ◽  
Ken Borrelli ◽  
Matthew Grisewood ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Structure Prediction ◽  
Heavy Atom ◽  
Accurate Solution ◽  
Binding Modes ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Test Set ◽  
Cross Docking ◽  
Public Data

We present a reliable and accurate solution to the induced fit docking problem for protein-ligand binding by combining ligand-based pharmacophore docking (Phase), rigid receptor docking (Glide), and protein structure prediction (Prime) with explicit solvent molecular dynamics simulations. We provide an in-depth description of our novel methodology and present results for 41 targets consisting of 415 cross-docking cases divided amongst a training and test set. For both the training and test-set, we compute binding modes with a ligand-heavy atom RMSD to within 2.5 Å or better in over 90% of cross-docking cases compared to less than 70% of cross-docking cases using our previously published induced-fit docking algorithm and less than 41% using rigid receptor docking. Applications of the predicted ligand-receptor structure in free energy perturbation calculations is demonstrated for both public data and in active drug discovery projects, both retrospectively and prospectively.

scholarly journals Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein–Ligand Binding

2021 ◽  
Vol 17 (4) ◽  
pp. 2630-2639
Author(s):  
Edward B. Miller ◽  
Robert B. Murphy ◽  
Daniel Sindhikara ◽  
Kenneth W. Borrelli ◽  
Matthew J. Grisewood ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Accurate Solution ◽  
Induced Fit Docking ◽  
Induced Fit

scholarly journals A Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding

2020 ◽  
Author(s):  
Edward Miller ◽  
Robert Murphy ◽  
Daniel Sindhikara ◽  
Ken Borrelli ◽  
Matthew Grisewood ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Structure Prediction ◽  
Heavy Atom ◽  
Accurate Solution ◽  
Binding Modes ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Test Set ◽  
Cross Docking ◽  
Public Data

We present a reliable and accurate solution to the induced fit docking problem for protein-ligand binding by combining ligand-based pharmacophore docking (Phase), rigid receptor docking (Glide), and protein structure prediction (Prime) with explicit solvent molecular dynamics simulations. We provide an in-depth description of our novel methodology and present results for 41 targets consisting of 415 cross-docking cases divided amongst a training and test set. For both the training and test-set, we compute binding modes with a ligand-heavy atom RMSD to within 2.5 Å or better in over 90% of cross-docking cases compared to less than 70% of cross-docking cases using our previously published induced-fit docking algorithm and less than 41% using rigid receptor docking. Applications of the predicted ligand-receptor structure in free energy perturbation calculations is demonstrated for both public data and in active drug discovery projects, both retrospectively and prospectively.

scholarly journals A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein

2011 ◽  
Vol 7 (5) ◽  
pp. e1002054 ◽  
Author(s):  
Daniel-Adriano Silva ◽  
Gregory R. Bowman ◽  
Alejandro Sosa-Peinado ◽  
Xuhui Huang
Keyword(s):  
Ligand Binding ◽  
Induced Fit ◽  
Conformational Selection
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