Structure determination, refinement, and validation

Abstract

It can be a tremendous advantage to have the X-ray crystal structure of a protein that is targeted for drug discovery. Due to recent advances in methods, software and hardware, crystallographic structure determination no longer requires a specialist in the method, but rather it has become a technique that can be readily applied to many research problems. The high-throughput approaches developed and used by structural genomics projects can be adapted and used to aid drug discovery efforts. It should be emphasized, however, that one cannot blindly accept the results of automated approaches and that it is essential to carefully validate the model, which is the interpretation of the observed electron density. It is important to be sure that it correctly describes the structure. The investigator that wishes to make use of the extensive database of protein structures in the Protein Data Bank (PDB) also needs to be know how to evaluate structural models, understand how they are related to the experimental data and be able to utilize computer graphics programs to look at the electron density distribution together with the model.