W0317

Sequence Docking, Rotamer Assignment And Real Space Torsional Refinement in ARP/wARP. S.X. Cohen, M. Kakaris, R. Morris, V. Lamzin & A. Perrakis, Molecular Carcinogenesis, The Netherlands Cancer Institut, Plesmanlaan 121, Amsterdam, 1066 CX THE NETHERLANDS.

In recent years, manual interactive building of protein structure models (using software like O, XtalView, Quanta or MAIN) is gradually superseded by automated procedures, such as ARP/wARP, Resolve or MAID. In both cases, the first step of the modelling is to build main chain fragments; the next important step is to assign amino acid type information to each residue of the main chain using the available sequence information of the protein (often termed 'docking' the fragments in sequence) and use this information to build amino acid side chains. The docking step helps to increase the completeness of the model (typically half of the atoms of the protein are in side chains) but also to increase the number of restraints for subsequent refinement.

We demonstrate an algorithm which is able to dock main chain fragments within a known sequence. This algorithm uses main chain coordinates and (in the current implementation) free atoms to model the rest of the electron density map (other modules directly using electron density maps are under development) and is able to handle the presence of NCS. This algorithm has been implemented in C++ using a library style design so that it can be used in automated building procedures as well as included in interactive building programs (ie. 3D-CCP4) to help the user to take decisions on sequence docking.

The side chain of each amino acid is then build in the current electron density map using templates from the Richardson's rotamer database. Finally, real space torsional refinement of side chains is performed to optimise the atom positions with limited geometrical distortions. The same design choice has been made for this part of the protocol (C++ library), with the addition of providing versatile scoring targets for both rotamer assignment and refinement (electron density at atomic centres; closest neighbour, interpolation; real space electron density correlation).