HipHop Refinement of Protein Structures

Jan Ondráček

Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16637 Prague 6

A novel multisolution refinement method for protein diffraction data is described. HipHop refinement explores the conformational landscape by modification of the phases by introduction of water molecules into the model, followed by many cycles of refinement and removal of water molecules that do not comply with a minimal electron density, ball shape and a distance from protein. The resulting ensemble of generated models represents the graphical expression of structural variances of the crystal structure. The shape of the distribution function (histogram) of clusters (arising by overlapping of models) of water molecules expresses the probability of the correctness of the refinement. The method was successfully used for refinements of many protein crystal structures, e.g. lysozyme soaked with periodate [1] or bromate [2]. Noteworthy, the integrity of this approach was recently corroborated by Furnham et al. [3]. The general paper is in preparation [4]. Program versions for Shelx and Refmac are available free on http://www.img.cas.cz/hiphop.

1. Ondráček, J., Weiss, M.S., Brynda, J., Fiala, J., Jursík, F., Řezáčová, P., Jenner, L.B. & Sedláček, J. (2005). Acta Crystallogr. D61, 1181-1189.
2. Ondráček^, J. & Mesters J.R. (submitted to print). Acta Crystallogr. D.
3. Furnham, N., Blundell, T.L., DePristo, M.A., Terwilliger, T.C. (2006). Nature Struct. Mol. Biol. 13, 184-185.
4. Ondráček, J., Weiss, M.S., Hilgenfeld, R., Sedláček. J. & Mesters,J. (manuscript in preparation). Structure.