WFU Physics Colloquium

TITLE: Clustering functionally relevant space at the molecular level: subfamily classification and functional mechanism in the peroxiredoxin protein family

SPEAKER: Dean Jacquelyn S. Fetrow ,

TIME: Wednesday Dec. 1, 2010 at 4:00 PM

PLACE: Room 101 in Olin Physical Laboratory

Genome sequencing projects have resulted in tremendous quantities of sequence information, but experimental characterization of protein function has been performed on only a small fraction of sequences. Although numerous computational methods exist that provide functional classification for many uncharacterized proteins, misannotation is a significant problem, since most sequence-focused methods are unable to distinguish the features of individual subfamilies. A recently developed method called Deacon Active Site Profiling (DASP) is able to extract the features located near the functional site of structurally characterized proteins and utilize this information to identify other proteins in the sequence database that share similar functional site characteristics. This method is used to analyze the widely distributed and moderately well-characterized peroxiredoxin protein family; family members detoxify hydrogen peroxide and other oxidized molecules in the cell. Over 3500 putative peroxiredoxin sequences were identified from the sequence database and classified into one of six subfamilies. Subfamily searches using DASP were highly specific and allowed identification of key features at the active site of each subfamily, providing a number of experimentally testable hypotheses. This work paves the way for assignment of sequences from other large protein families to subfamilies with a reasonable degree of accuracy.