Extend-NMR: Extending NMR for Functional and Structural Genomics
Partner 6: Institute of Biophysics and physical Biochemistry, University of Regensburg
People involved: Konrad Brunner¹, Tobias Harsch¹, Harald Donaubauer¹, Wilhelm Malloni¹, Silvia de Sanctis¹, Kumaran Baskaran¹, Bärbel Kieninger¹, Wolfram Gronwald², Klaus-Peter Neidig³ and Hans Robert Kalbitzer¹
¹Institute of Biophysics and Physical Biochemistry, University of Regensburg
²Institute of functional genomic, University of Regensburg
³Bruker BioSpin GmbH, Software Department

AUREMOL:Automatic protein structure determination from NMR data

Several approaches to the problem of automated protein structure determination from NMR data exist. They can be divided into classic bottom-up strategies that make use of a large base of experimental data and top-down approaches that try to minimize the experimental effort and concentrate on the structure part. For the bottom-up class of programs a strong focus is put on obtaining a complete sequential assignment. Obviously the inherent drawback in this approach is the experimental effort involved in obtaining the required spectra.

In a top-down approach the focus shifts to the structure itself. The concept for automation is a molecule centered top-down approach where all of the available a priori information is used to eliminate as many free parameters as possible and reduce the amount of experimental data to a minimum. Along the way, any need for expert intervention is also to be reduced to a minimum

Therefore we are developing AUREMOL (www.auremol.de), which goal is the reliable and automatic structure determination of biological macro molecules such as proteins from NMR data (1). The goal is to deliver an extensive tool for protein structure determination from NMR data that speeds up and automates this process. AUREMOL currently relies on external software only for raw data processing and restrained molecular dynamics calculations. It offers routines and utilities for the data analysis and structure validation steps in one NMR program with an emphasis on NOESY evaluation. Advanced modules of AUREMOL include the spectrum simulation module RELAX (1), the sequential assignment algorithm ASSIGN (2), the NOESY assignment tool KNOWNOE (1), the distance calculation module REFINE (3) and the structure evaluation module RFAC (1).

Fig.1: Iterative structure determination
(1) Gronwald, W. and Kalbitzer, H.R., 2004, Progr. NMR Spectr. 44, 33-96
(2) Brunner, K., 2006, Universität Regensburg, Dissertation
(3) Trenner, J.M., 2006, Universität Regensburg, Dissertation

AUREMOL Features

  • Peak picking (CCPN accessible)
  • Volume calculation (CCPN accessible)
  • Sequential assignment (ASSIGN)
  • NOESY spectra assignment (KNOWNOE)
  • Shifts adaption to spectrum (SHIFTOPT)
  • NOESY Assignment (KNOWNOE)
  • Spectrum simulation (RELAX)
  • Distance calculation (REFINE)
  • Molecular dynamics interface (MDI)
  • Structure validation (RFAC)
  • Intelligent Structural Information Combination (ISIC)
  • Homology Modelling (PERMOL)
  • Powerful tools and converters for data handling

Fig. 2. Modules in AUREMOL