Contributions of Structure Comparison Methods to the Protein Structure Prediction Field

Since their development, structure comparison methods have contributed to advance our understanding of protein structure and evolution (Greene et al, 2007; Hasegawa & Holm, 2009), to help the development of structural genomics projects (Pearl et al, 2005), to improve protein function annotations (D. A. Lee et al), etc, thus becoming an essential tool in structural bioinformatics. In recent years, their application range has grown to include the protein structure prediction field, were they are used to evaluate overall prediction quality (Jauch et al, 2007; Venclovas et al, 2001; Vincent et al, 2005; G. Wang et al, 2005), to identify a protein’s fold from low-resolution models (Bonneau et al, 2002; de la Cruz et al, 2002), etc. In this chapter, after briefly reviewing some of these applications, we show how structure comparison methods can also be used for local quality assessment of low-resolution models and how this information can help refine/improve them. Quality assessment is becoming an important research topic in structural bioinformatics because model quality determines the applicability of structure predictions (Cozzetto et al, 2007). Also, because prediction technology is now easily available and potential end-users of prediction methods, from template-based (comparative modeling and threading) to de novo methods, are no longer specialized structural bioinformaticians. Quality assessment methods have been routinely used for many years in structural biology in the evaluation of experimental models. These methods focus on several features of the protein structure (see (Laskowski et al, 1998) and (Kleywegt, 2000) and references therein). Because a number of quality issues are common to both experimental and predicted models, the use of these methods has been naturally extended to the evaluation of structure predictions. For example, in the case of homology modeling, a widely used structure prediction technique, evaluation of models with PROCHECK (Laskowski et al, 1993), WHAT-CHECK (Hooft et al, 1997), PROSA (Sippl, 1993), and others (see (Marti-Renom et al, 2000) and references therein) is part of the standard prediction protocol; WHATIF (Vriend, 1990) and PROSA (Sippl, 1993) have also been used in the CASP experiment to assess comparative models (Venclovas, 2001; Williams et al, 2001); etc. Some quality assessment problems are unique to the structure prediction field, given the specific characteristics of computational models, and have led to the development of