Low Resolution Refinement and Automated Model Building

Automated model building and refinement methods with ARP/wARP have progressed at many levels (Partners 1A and 6), from some basic recognition algorithms to the improved communication between all the programs involved, including those dealing with molecular replacement.

The effectiveness of model refinement at low resolution in the context of the ARP/wARP suite, has been enhanced Partner 6 with an introduction of a novel use of restraints. The approach taken makes use of the implementation of flexible, user-specified restraints in the REFMAC refinement program. From within ARP/wARP, restraints are automatically formulated for its hybrid model, consisting of part protein model, part free atom model. The restraints for the free atoms promote "general" protein geometry amongst the free atoms, as well as extend the geometric features of the protein model into the free atom model. A prototype of a program to generate these restraints and its interfacing with REFMAC has been developed.

To complement this work, Partner 8 has added pseudo-restraints into the refinement program REFMAC to enable refinement of yet chemically unidentified structures. It now can handle many types of chemical information including bonds, angles, torsions and planarities. These restraints allow a smooth transition from electron density to full atomic model, and thus enhance the chance of success of automatic model building and refinement, Figure 3.10.a.

Figure 3.10.a. Model building with ARP/wARP. Left - the current release, version 7.0. Right - the version with implementation of the conditional restraints.