Optimal contact definition for reconstruction of contact maps.
BACKGROUND
Contact maps have been extensively used as a simplified representation of protein structures. They capture most important features of a protein's fold, being preferred by a number of researchers for the description and study of protein structures. Inspired by the model's simplicity many groups have dedicated a considerable amount of effort towards contact prediction as a proxy for protein structure prediction. However a contact map's biological interest is subject to the availability of reliable methods for the 3-dimensional reconstruction of the structure.


RESULTS
We use an implementation of the well-known distance geometry protocol to build realistic protein 3-dimensional models from contact maps, performing an extensive exploration of many of the parameters involved in the reconstruction process. We try to address the questions: a) to what accuracy does a contact map represent its corresponding 3D structure, b) what is the best contact map representation with regard to reconstructability and c) what is the effect of partial or inaccurate contact information on the 3D structure recovery. Our results suggest that contact maps derived from the application of a distance cutoff of 9 to 11A around the Cbeta atoms constitute the most accurate representation of the 3D structure. The reconstruction process does not provide a single solution to the problem but rather an ensemble of conformations that are within 2A RMSD of the crystal structure and with lower values for the pairwise average ensemble RMSD. Interestingly it is still possible to recover a structure with partial contact information, although wrong contacts can lead to dramatic loss in reconstruction fidelity.


CONCLUSIONS
Thus contact maps represent a valid approximation to the structures with an accuracy comparable to that of experimental methods. The optimal contact definitions constitute key guidelines for methods based on contact maps such as structure prediction through contacts and structural alignments based on maximum contact map overlap.
Duarte
Jose M
JM
Max Planck Institute for Molecular Genetics, Ihnestr, Berlin, Germany. duarte@molgen.mpg.de
Sathyapriya
Rajagopal
R
Stehr
Henning
H
Filippis
Ioannis
I
Lappe
Michael
M
D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
D011506:Proteins