The description of protein internal motions aids selection of ligand binding poses by the INPHARMA method
- Author(s)
- B. Stauch, J. Orts, T. Carlomagno
- Abstract
Protein internal motions influence observables of NMR experiments. The effect of internal motions occurring at the sub-nanosecond timescale can be described by NMR order parameters. Here, we report that the use of order parameters derived from Molecular Dynamics (MD) simulations of two holo-structures of Protein Kinase A increase the discrimination power of INPHARMA, an NMR based methodology that selects docked ligand orientations by maximizing the correlation of back-calculated to experimental data. By including internal motion in the back-calculation of the INPHARMA transfer, we obtain a more realistic description of the system, which better represents the experimental data. Furthermore, we propose a set of generic order parameters, derived from MD simulations of globular proteins, which can be used in the back-calculation of INPHARMA NOEs for any protein–ligand complex, thus by-passing the need of obtaining system-specific order parameters for new protein–ligand complexes.
- Organisation(s)
- External organisation(s)
- European Molecular Biology Laboratory
- Journal
- Journal of Biomolecular NMR
- Volume
- 54
- Pages
- 245-256
- No. of pages
- 12
- ISSN
- 0925-2738
- DOI
- https://doi.org/10.1007/s10858-012-9662-1
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106002 Biochemistry, 106006 Biophysics
- Keywords
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/64446702-64e1-4fd8-9ea1-f9f8e031658a