Solving Protein Structures Using Molecular Replacement Via Protein Fragments

The need to determine phases is a major bottleneck in a fully automated X-ray crystallography pipeline. The problem commonly called phasing can be solved by a computational method called molecular replacement (MR). With the deposition of more and more proteins into the Protein Data Bank (PDB), it has been shown that the MR yields better initial models. In this paper, ab initio first model generation is addressed. A novel scheme using PHASER is proposed which does not require any a priori information about the structure. The input to the system is the target structure factors and the sequence. We created a unique set of supersecondary structure (fragment) dataset and used them in creation of the first model. The method was evaluated with log-likelihood gain (LLG) and translational Z-score (TFZ) as defined by PHASER. The results obtained are highly encouraging with translation Z-scores of 7 and above for the first model. The proposed scheme is tested on six proteins, two each from α, β and α+ β classes with very good results.