Protein Structure and Function: Applications of Bioinformatics Methods - John Rigden 2014

Spatial Motifs
Conclusion

Structure/135.html">Structural motifs are patterns of local Cell/13.html">Protein Structure typically associated with protein function, relying on residues within binding sites or catalytic centers. Over the course of evolution, Proteins may diverge by accumulating random Mutations that do not disrupt their function while preserving the structural components critical to it. Ideally, a structural motif should encompass precisely these functionally critical structural components, serving as a sensitive and specific indicator of function. Numerous Methods have been developed to identify structural motifs and search for them within protein structures. However, compared to algorithmic advancements, less success has been achieved in establishing accessible, searchable Databases of structural motifs that are both functionally specific and broadly comprehensive. The number of unannotated structures is bound to grow, especially with the inclusion of those generated by comparative modeling (see Chapter 3). Challenges include developing functional descriptors and a detailed structure-function Classification in a machine-readable format that avoids loss of precision or meaning, as well as creating semi-automated and automated methods to integrate the continuous influx of new sequences and structures into these databases.

Acknowledgments. We are grateful for the support provided by NIH GM60595 and NSF DBI-0234768. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). We thank Jacqueline Fetrow and Stacy Nutson (Wake Forest University) for providing Figure 8.3 as an example of results generated by the FFF/DASP/PASSS motif analysis software.