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

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 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.

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

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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