Protein structure modeling

Sanchez K and A Sali 1998. Large-scale Protein Structure Modelling of the Saccharomyces cerevi. Genome. Proceedings of the National Academy of Sciences USA 95 13597-13602. 

Figure 1 The basis of comparative protein structure modeling. Comparative modeling is possible because evolution resulted in families of proteins, such as the flavodoxin family, modeled here, which share both similar sequences and 3D structures. In this illustration, the 3D structure of the flavodoxin sequence from C. crispus (target) can be modeled using other structures in the same family (templates). The tree shows the sequence similarity (percent sequence identity) and structural similarity (the percentage of the atoms that superpose within 3.8 A of each other and the RMS difference between them) among the members of the family.

Although comparative modeling is the most accurate modeling approach, it is limited by its absolute need for a related template structure. For more than half of the proteins and two-thirds of domains, a suitable template structure cannot be detected or is not yet known [9,11]. In those cases where no useful template is available, the ab initio methods are the only alternative. These methods are currently limited to small proteins and at best result only in coarse models with an RMSD error for the atoms that is greater than 4 A. However, one of the most impressive recent improvements in the field of protein structure modeling has occurred in ab initio prediction [155-157]. 

Comparative Protein Structure Modeling VIII. CONCLUSION... 

We are grateful to Dr. Azat Badretdinov and Mr. Eric Feyfant for many discussions about comparative protein structure modeling. AF is a Burroughs Wellcome Fellow. RS is a Howard Hughes Medical Institute predoctoral fellow. FM is a Norman and Rosita Winston Biomedical Research Foundation Fellow. AS is a Sinsheimer Scholar and an Alfred P. Sloan Research Fellow. The investigations have also been aided by grants from NIH (GM 54762) and NSF (BIR-9601845). 

R Sanchez, A Sail. Large-scale protein structure modeling of the Saccharomyces cerevisiae genome. Proc Natl Acad Sci USA 95 13597-13602, 1998. 

Renom. MODELLER, A Protein Structure Modeling Program, Release 5. 1999. http // guitar.rockefeller.edu/... 

R Sanchez, A Sail. Evaluation of comparative protein structure modeling by MODELLER-3. Pi otems Suppl 1 50-58, 1997. 

R Sanchez, A Sail. ModBase A database of comparative protein structure models. Biomfor-matics 15 1060-1061, 1999. 

Marti-Renom MA et al (2000) Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29 291-325... 

Back, J.W. et al. (2003) Chemical cross-linking and mass spectrometry for protein structural modeling. J. Mol. Biol. 331, 303-313. 

Sanchez, R., and Sali, A. (1997). Advances in comparative protein-structure modelling. Curr. Opin. Struct. Biol. 7, 206-214. 

Fiser A, Sali A. 2003. Modeller generation and refinement of homology-based protein structure models. Methods Enzymol 374 461-491. 

The number of experimentally known structures is also increasing, and comparative modeling is likely to play an increasing role in protein structural modeling in the future. 

C. B. Anfinsen, The genetic control of tertiary protein structure. Model systems, Cold Spring Harbor Symp. Quant. Biol. 

Figure 4 Steps in homology modeling of protein structure. Modeling the structure of a protein by considering its homology to known homologs is one of the most effective methods of structure-prediction. The critical steps are the identification and alignment of the target sequence to the template sequence (1) and (2).

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