Empirical limits for template-based protein structure prediction: the CASP5 example

Most protein structure prediction methods use templates to assist in the construction of protein models. In this paper, we analyse the current state of template-based modelling approaches and reach an estimate of the empirical limits of these methods. Our analysis show that current prediction methods are already reaching these empirical accuracy limits in the easier cases, where finding a close homologue to the native target structure is not a problem. However, we find that even in the absence of alignment errors and using optimal templates, template-based methods have intrinsic limitations, suggesting that other methodologies, such as ab initio procedures, must be used if accuracy is ultimately to be improved.