INPHARMA exploits inter-ligand NOEs occuring between two ligands binding competetively to the same target protein. These NOEs appear as cross-peaks in the NOESY spectrum and is meadiated by the receptor protein.
INPHARMA-NOEs can be theoretically estimated, e.g. on pairs of protein-ligand docking modes generated by computational routines.
Evaluating the agreement between theoretical and experimental INPHARMA-NOEs we can distinguish between docking modes that does not fit the experimental data.
- "The INPHARMA Method: Protein-Mediated Interligand NOEs for Pharmacophore Mapping" [Link] in Angewandte Chemie.
- "The INPHARMA technique for pharmacophore mapping: A theoretical guide to the method" [Link] in the Journal of Magnetic Resonance.
New software for the analysis and quantitative evaluation of INPHARMA-NOEs have recently been developed. In the spINPHARMA package suite we provide:
- spINPHARMA - a C++ program for the quantitative evaluation of experimental vs theoretical NOE data.
- spINPHARMA-R - an R-package with functionality for visualzing and evaluating INPHARMA data.
- a PyMOL plugin for the preparation of structure files.
The spINPHARMA package suite is free of charge for academic institutions. Obtain immediately your copy by sending an email to our software request email.
See also our INPHARMA-Wiki here for tutorials, installation instructions, and manuals.
spINPHARMA is free software for academic institutions for non-profit work.
The INPHARMA technique has the major advantage that it is not limited by the protein size or availability of isotope-labeled protein. The technique requires low affinity ligands, making it attractive for fragment-based studies and lead generation.
See "Selected Publications" for more applications of INPHARMA.
An R-package for the analysis and visualization of INPHARMA data is released. Please see the Wiki for user examples.
- "The INPHARMA Method: Protein-Mediated Interligand NOEs for Pharmacophore Mapping". [Link]
Sánchez-Pedregal VM, Reese M, Meiler J, Blommers MJJ, Griesinger C, Carlomagno T, Angewandte Chemie, 2005, 117(27):4244-47.
- "Structural basis of the activity of the microtubule-stabilizing agent epothilone a studied by NMR spectroscopy in solution".[Link]
Reese M, Sánchez-Pedregal VM, Kubicek K, Meiler J, Blommers MJJ, Griesinger C, Carlomagno T Angewandte Chemie, 2007, 46(11):1864-8.
- "Crystallography-Independent Determination of Ligand Binding Modes". [Link]
Orts J, Tuma J, Reese M, Grimm K, Monecke P, Bartoschek S, Schiffer A, Wendt U, Griesinger C, Carlomagno T, Angewandte Chemie, 2008, 47(40):7736–40.
- "The INPHARMA technique for pharmacophore mapping: A theoretical guide to the method". [Link]
Orts J, Griesinger C, Carlomagno T, Journal of Magnetic Resonance, 2009, 200(1):64-73.
- "INPHARMA-based identification of ligand binding site in fragment-based drug design". [Link]
Krimm I, MedChemComm, 2012, 3:605-610.
- "Accounting for conformational variability in protein-ligand docking with NMR-based rescoring". [Link]
Skjaerven L*, Codutti L*, Angelini A, Grimaldi M, Latek D, Monecke P, Dreyer M, Carlomagno T, J Am Chem Soc, 2013, 135(11):4403-11.
INPHARMA was partly financed by the German Federal Ministry of Education and Research