Protein Folding Problems and Functional Sites

PROTEIN FOLDING PROBLEMS AND FUNCTIONAL SITES 12.2.1. Fold Recognition and Structure Alignment 

Each amino acid has distinct attributes such as size, hydrophobicity/hy-drophilicity, hydrogen bonding capacity, and conformational preferences that allow it to contribute to a protein fold. Attempts are being made to interpret the protein fold in terms of amino acid descriptors. Structural alignments are more accurate than sequence alignments, and the local physicochemical environment of every residue within each 3D structure is directly obtainable (e.g., AAindex at http //www. 

A classification system, such as SCOP (Lesk and Chothia, 1984), categorizes structure domains based on secondary structural elements within a protein into a. structure (made up primarily from a helices), / structure (made up primarily from / strands), a// structure (comprised of primarily P strands alternating with a helices), and a + P structure (comprised of a mixture of isolated a helices and / strands). In this classification (Brenner et al, 1996 Lesk, 1991), only the core of the domain is considered. Therefore, it is possible for an all-a structure to have very small amount of p strand outside the a-helical core. Similarly, an all-/ protein may have a small presence of a or 310 helix. The SCOP (http //scop.mrc-lmb.cam.ac.uk/scop/) can be summarized as follows  

For individual pairs of interacting helices, certain regularities in the patterns of tertiary-structural interactions between pairs of helices have been observed. 

The CATH protein domain database (http //www.biochem.ucl.ac.uk/bsm/cath) is a hierarchical classification of protein domain structures into evolutionary families and structural groupings depending on sequence and structure similarity (Pearl et al, 2000). The protein domains are classified according to four major levels. 

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