With Feng Cui, Hanah Mahan, kriti Mukhopadhyay, Rahul Ravindrudu, Kyoungmin Roh, Steve Smith, Di Wu, wonbin young, ...

Protein structures, determined either theoretically or experimentally, always require further refinement. A major computational tool for structure refinement is energy minimization. Since energy minimization is limited for obtaining globally optimal structures, additional conformational constraints are always helpful for improving the structures beyond simple energy minimization. We have conducted extensive statistical analysis on protein inter-atomic distances and profiled the distributions of the distances of various types in databases of known protein structures. We have then developed constraints for the distances based on their database distributions and applied them to structure refinement.

Protein structure refinement

The NMR structures of protein 2IGG are refined with (green line) and without (red line) additional database distance constraints, and compared against the X-ray crystal structure  (blue line).

We have been able to refine a set of NMR-determined protein structures successfully by using the database derived distance constraints (in addition to the original NMR distance data). 

 

We have applied the database derived distance constraints to refining the underdetermined loop regions of the prion protein E200K. After the refinement, the percentage of the residues of the protein in the most favorable regions of the Ramachandran plot was improved significantly from 85% to 90%.

  

We have also developed distance-based mean-force potentials using  the database distributions of the distances, which can be used to refine structures even more effectively. 

Phone: 515-294-8165

Fax: 515-294-5454

E-mail: zhijun@iastate.edu

Contact information: