‘Fast protein fold determination using structure prediction algorithms incorporating easily accessible NMR data’

Angel Ramírez Ortiz, Carlos González Ibañez, Jesús Villajos Barja, Jorge Santoro Said, Manuel Rico Sarompas, Mª Angeles Jiménez, Pablo Sanz Mercado.

The goal of the present research project is to develop fast, automatic, low-resolution protein structure determination methods suitable for large scale structural genomics applications. On the bioinformatic side, this goal will be addressed through the following sequential steps: (1) creation of a library of rigid protein building blocks and domains by means of automatic structural classification algorithms; (2) building block recognition using threading methods incorporating chemical shifts and/or residual dipolar couplings, that is, development of a threading method able to detect the most likely three dimensional conformation of a input (experimental) set of chemical shifts and/or residual dipolar couplings from the building block database; (3) derivation of three dimensional restraints from the matches, to be used within protein folding algorithms in order to determine a low-resolution fold structure; (4) all-atom rebuilding, refinement with molecular dynamics and integration with automatic NOE assignment tools for automatic structural refinement. On the NMR side, an exploration and testing of current and new anisotropocic media used to partially align protein molecules within the magnetic field so as to determine residual dipolar couplings will be carried out, together with the implementation of automatic methods of NMR data analysis.