1. Protein structure Friday, 10 February 2006 Introduction to Bioinformatics Brigham Young University DA McClellan david_mcclellan@byu.edu

2. Classical structural biology Determine biochemical activity Purify protein Determine structure Understand mechanism, function Fig. 9.1 Page 274

3. Structural genomics Determine genomic DNA sequence Predict protein Determine structure or analyze in silico Understand mechanism, function Fig. 9.1 Page 274

4. Structural genomics A goal of structural genomics is to determine protein structures that span the full extent of sequence space. Page 273

5. Protein function and structure Function is often assigned based on homology. However, homology based on sequence identity may be subtle. Consider RBP and OBP: these are true homologs (they are both lipocalins, sharing the GXW motif). But they are distant relatives, and do not share significant amino acid identity in a pairwise alignment. Protein structure evolves more slowly than primary amino acid sequence. RBP and OBP share highly similar three dimensional structures. Page 274

6. Principles of protein structure Primary amino acid sequence Secondary structure:  helices,  sheets Tertiary structure: from X-ray, NMR Quaternary structure: multiple subunits Page 276