PREDICTION OF PROTEIN STRUCTURE IN 1D: SECONDARY STRUCTURE, MEMBRANE REGIONS, AND SOLVENT ACCESSIBILITY
No General Prediction of 3D Structure from Sequence, Yet
The hypothesis that the 3D structure1 of a protein (the fold) is uniquely determined by the specificity of the sequence has been verified for many proteins (Anfinsen, 1973). While particular proteins (chaperones) often play an important role in folding (Ellis, Dobson, and Hartl, 1998), it is still generally assumed that the final structure is at the free-energy minimum (Dobson and Karplus, 1999). Thus, all information about the native structure of a protein is coded in the amino acid sequence and its native solution environment. Can we decipher the code; that is, can we predict 3D structure from sequence? In principle, the code could by deciphered from physicochemical principles (Levitt and Warshel, 1975; Hagler and Honig, 1978). In practice, the inaccuracy in experimentally determining the basic parameters and the limited computing resources prevent prediction of protein structure from first principles (van Gunsteren, 1993). Hence, the only successful structure prediction tools are knowledge-based, using a combination of statistical theory and empirical rules. The field of protein structure prediction has advanced significantly over the past 15 years (see Chapter 28) with improved methods (Kryshtafovych et al., 2005; Moult et al., 2005). However, possibly the most important change was the ...