NAME: Serge Cohen

AFFILIATION: NKI, Amsterdam, Holland

CONTACT: s.cohen@nki.nl

 

TITLE: "ARP/wARP and molecular replacement: The Next Generation"

ABSTRACT: Serge X Cohen, Marouane Ben Jelloul, Puck Knipscheer, Joyce Kebbink, Victor S Lamzin, Anastassis Perrakis.

 

As the number of structure deposited in the PDB increases it is more and more frequent to be able to solve a structure using Molecular Replacement. A large effort is currently underway to enable the molecular replacement method to work with search models that are either partial (especially in the context of macromolecular complexes) or of low identity to the structure in question.

 

We demonstrate how ARP/wARP is used to remove a significant part of the so-called 'model bias' produced by the molecular replacement technique and construct a nearly complete model. There are two extreme treatments of the starting model: one can remove all chemical restraints from the start; in the opposite end one can keep the chemical identity of all atoms (as provided by the search model) and only remove atoms on the basis of electron density during refinement. These procedures and a few variants are explained.

 

Finally we show a set of three examples. The first one demonstrates how ARP/wARP is able to complete a structure which was solved with a very partial search model, at moderate resolution. The second one exemplifies the ability of ARP/wARP to recover from a very poor starting phase set in a difficult case of molecular replacement starting from an NMR model, provided that the amount and quality of observations are sufficient. The last example deals with the combination of ARP/wARP and NCS density averaging to enhance further the completeness of the automatically produced model.