Related ArticlesOn-the-Fly Integration of Data from a Spin-Diffusion-Based NMR Experiment into Protein-Ligand Docking.
J Chem Inf Model. 2015 Jul 30;
Authors: Onila I, Ten Brink T, Fredriksson K, Codutti L, Mazur A, Griesinger C, Carlomagno T, Exner TE
Abstract
INPHARMA (Internuclear NOEs for Pharmacophore Mapping) determines the relative orientation of two competitive ligands in the protein binding pocket. It is based on the observation of interligand transferred NOEs mediated by spin diffusion through protons of the protein and is, therefore, sensitive to the specific interactions of each of the two ligands with the protein. We show how this information can be directly included into a protein-ligand docking program to guide the prediction of the complex structures. Agreement between the experimental and back-calculated spectra based on the full relaxation matrix approach is translated into a score contribution that is combined with the scoring function ChemPLP of our docking tool PLANTS. This combined score is then used to predict the poses of 5 weakly bound cAMP-dependent Protein Kinase (PKA) ligands. After optimizing the setup, which finally also included trNOE data and optimized protonation states, very good success rates were obtained for all combinations of three ligands. For one additional ligand, no conclusive results could be obtained due to the ambiguous electron density of the ligand in the X-ray structure, which does not disprove alternative ligand poses. The failures of the remaining ligand are caused by suboptimal locations of specific protein side chains. Therefore, side-chain flexibility should be included in an improved INPHARMA-PLANTS version. This will reduce the strong dependence on the used protein input structure leading to improved scores not only for this last ligand.
PMID: 26226383 [PubMed - as supplied by publisher]
[NMR paper] Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)
Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)
Publication date: Available online 23 March 2015
Source:Journal of Magnetic Resonance</br>
Author(s): David S. Snyder , Mihaela Chantova , Saadia Chaudhry</br>
NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained...
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03-25-2015 10:15 AM
[NMR paper] Accounting for Conformational Variability in Protein-Ligand Docking with NMR-Guided Rescoring.
Accounting for Conformational Variability in Protein-Ligand Docking with NMR-Guided Rescoring.
Related Articles Accounting for Conformational Variability in Protein-Ligand Docking with NMR-Guided Rescoring.
J Am Chem Soc. 2013 Apr 8;
Authors: Skjærven L, Codutti L, Angelini A, Grimaldi M, Latek D, Monecke P, Dreyer MK, Carlomagno T
Abstract
A key component to success in structure-based drug design is reliable information on protein-ligand interactions. Recent development in NMR techniques has accelerated this process by overcoming some of...
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04-10-2013 07:21 PM
Accounting for Conformational Variability in Protein–Ligand Docking with NMR-Guided Rescoring
Accounting for Conformational Variability in Protein–Ligand Docking with NMR-Guided Rescoring
Lars Skjærven, Luca Codutti, Andrea Angelini, Manuela Grimaldi, Dorota Latek, Peter Monecke, Matthias K. Dreyer and Teresa Carlomagno
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja4007468/aop/images/medium/ja-2013-007468_0009.gif
Journal of the American Chemical Society
DOI: 10.1021/ja4007468
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/39zhOcXGgnI
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04-09-2013 06:22 AM
[NMR paper] Electron Spin Density on the Axial His Ligand of High-Spin and Low-Spin Nitrophorin 2 Probed by Heteronuclear NMR Spectroscopy.
Electron Spin Density on the Axial His Ligand of High-Spin and Low-Spin Nitrophorin 2 Probed by Heteronuclear NMR Spectroscopy.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Electron Spin Density on the Axial His Ligand of High-Spin and Low-Spin Nitrophorin 2 Probed by Heteronuclear NMR Spectroscopy.
Inorg Chem. 2013 Jan 17;
Authors: Abriata LA, Zaballa ME, Berry RE, Yang F, Zhang H, Walker FA, Vila AJ
Abstract
The electronic structure of heme proteins is exquisitely tuned...
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02-03-2013 10:19 AM
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
J Mol Graph Model. 2011 Sep 3;
Authors: Fukunishi Y, Mizukoshi Y, Takeuchi K, Shimada I, Takahashi H, Nakamura H
Abstract
We developed a new protein-ligand docking calculation method using experimental NMR data. Recently, we proposed a novel ligand epitope-mapping experiment, which utilizes the difference between the longitudinal relaxation rates of ligand protons with and...
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09-24-2011 04:11 PM
[NMR paper] Analysis of protein/ligand interactions with NMR diffusion measurements: the importan
Analysis of protein/ligand interactions with NMR diffusion measurements: the importance of eliminating the protein background.
Related Articles Analysis of protein/ligand interactions with NMR diffusion measurements: the importance of eliminating the protein background.
J Magn Reson. 2002 Apr;155(2):217-25
Authors: Derrick TS, McCord EF, Larive CK
Pulsed-field gradient nuclear magnetic resonance (PFG-NMR) is a well-established method for the determination of translational diffusion coefficients. Recently, this method has found applicability in...
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11-24-2010 08:49 PM
[NMR paper] Docking multiple conformations of a flexible ligand into a protein binding site using
Docking multiple conformations of a flexible ligand into a protein binding site using NMR restraints.
Related Articles Docking multiple conformations of a flexible ligand into a protein binding site using NMR restraints.
Proteins. 2002 Feb 15;46(3):295-307
Authors: Zabell AP, Post CB
A method is described for docking a large, flexible ligand using intra-ligand conformational restraints from exchange-transferred NOE (etNOE) data. Numerous conformations of the ligand are generated in isolation, and a subset of representative conformations is...
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[NMR paper] Structure prediction of protein complexes by an NMR-based protein docking algorithm.
Structure prediction of protein complexes by an NMR-based protein docking algorithm.
Related Articles Structure prediction of protein complexes by an NMR-based protein docking algorithm.
J Biomol NMR. 2001 May;20(1):15-21
Authors: Kohlbache O, Burchardt A, Moll A, Hildebrandt A, Bayer P, Lenhof HP
Protein docking algorithms can be used to study the driving forces and reaction mechanisms of docking processes. They are also able to speed up the lengthy process of experimental structure elucidation of protein complexes by proposing potential...
On-the-Fly Integration of Data from a Spin-Diffusion-Based NMR Experiment into Protein-Ligand Docking.
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