Hi, Molecular replacement gets progressively more difficult as the sequence identity drops, though the correlation between sequence identity and model quality is not perfect. With the best models having sequence identities around 24%, success is by no means guaranteed, so you might have to try lots of strategies or resort to experimental phasing. NMR models do tend to be worse for molecular replacement, so that will probably lower the chances of success further.
In addition to what others have said already, it's worth mentioning that, in a number of very difficult structure determinations (best models around 20% sequence identity), the key thing that made the difference between failure and success was pruning off the parts of the ensemble that do not agree among the members of the ensemble, leaving just the conserved core. This can be done, for instance, in the Ensembler program with the "trim=True" flag. For this to work best, it's helpful if you happen to have a number of potential models that are also relatively distantly related to each other, to really highlight what is conserved in the fold. Best wishes, Randy Read > On 29 Aug 2017, at 12:42, Andreas Forster <[email protected]> wrote: > > Dear Nishant, > > Rosetta is a good suggestion. You can also use an ensemble of several > related (superposed) structures as your search model. This will improve your > chances of success. > > All best. > > > Andreas > > > > On Tue, Aug 29, 2017 at 12:50 PM, Nishant Varshney <[email protected] > <mailto:[email protected]>> wrote: > Dear Crystallographers, > > I am working to solve an human protein structure which has a domain sequence > identity of 24% with domain of another protein. As Phaser as well as Molrep > failed to give any definite solution (TFZ=3.7 from MR), I want to ask, if > solution structure of another protein having domain sequence similarity of > 25% or a homology model can be used as a template for MR? > Many thanks and Regards > Nishant > > -- > Dr. Nishant Kumar Varshney, > Research Associate, > C/O Dr. Sameena Khan, > Drug Discovery Research Center, > Translational Health Science and Technology Institute (THSTI) > NCR Biotech Science Cluster, > 3rd Milestone, Faridabad – Gurgaon Expressway, > Faridabad – 121001 (HARYANA), India > Ph: +91- 0129-2876477 <tel:+91%20129%20287%206477> > Mob: 8390564690 > ------ Randy J. Read Department of Haematology, University of Cambridge Cambridge Institute for Medical Research Tel: + 44 1223 336500 Wellcome Trust/MRC Building Fax: + 44 1223 336827 Hills Road E-mail: [email protected] Cambridge CB2 0XY, U.K. www-structmed.cimr.cam.ac.uk
