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**Chapter 9** 

© 2012 Martínez-Castilla and Rodríguez-Sotres, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is

© 2012 Martínez-Castilla and Rodríguez-Sotres, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

properly cited.

**On the Assessment of Structural Protein** 

**Value, Potential and Limitations** 

León P. Martínez-Castilla and Rogelio Rodríguez-Sotres

improve the model. The limitations of the protocol are also discussed.

**2. The folding problem is a NP-hard problem involving a degenerate** 

As implied by the well-known Levinthal paradox (Levinthal, 1968), a full exploration of the entire conformational space theoretically available to a protein is out of the reach of current computational techniques. Equally unaccessible to nature is the sequence space available to polypeptide chains (Kono & Saven, 2001). Currently, the amount of available protein structures (the PDB) represents a fraction of the known protein amino acid sequences, and if the available sample is grouped in terms of different folds, the diversity in the PDB is even smaller. In addition, protein structure and function can tolerate a significant number of

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/47842

**1. Introduction** 

**informational code** 

**Models with ROSETTA-Design and HMMer:** 

The prediction of the three-dimensional structure of a protein, starting with the amino acid sequence, is still an unsolved issue. However a number of important advancements have been made and some methods offer solutions to this problem, specially when the target sequence has homologues whose structure has been determined. In any case, it is important to evaluate the quality of the prediction, as none of the methods offers assurance of success. The ROSETTA-design-HHMer (Rd.HMM) protocol stands out among the current quality assessment methods, because it offers evidence of the biological appropriateness of the prediction. In addition, Rd.HMM can be used to guide the modeling process towards the improvement of the model's quality. This chapter deals with the principles behind this protocol and gives practical advice on how to use the Rd.HMM to evaluate the quality of a three-dimensional modeled structure of a protein, and how to use the information to
