Extending the Reach of Molecular Replacement

摘要

Molecular replacement is already able to solve the majority of structures in the Protein Data Bank, thanks to the rapidly increasing number of template structures available and continuous improvements in the algorithms. Chances of success can be optimised by proper preparation of models, for instance by trimming poorly-conserved regions, creating an ensemble of alternative models or applying advanced homology modeling tools. The sensitivity of the molecular replacement search can be improved by using likelihood targets; these lend themselves to automation, which makes it possible to carry out extensive searches and helps to avoid user errors. The convergence radius of model completion can be extended by using methods that smoothly deform the starting model or apply advanced modeling techniques. Even more difficult structures can be solved by combining molecular replacement with other phasing methods, such as SAD phasing or multi-crystal averaging.