ABSTRACT
The aim of comparative or homology protein structure modeling is to build a three-dimensional (3D) model for a protein of unknown structure (the target) based on one or more related proteins of known structure (the templates) (Fig. 1) [1-6]. The necessary conditions for getting a useful model are that the similarity between the target sequence and the template structures is detectable and that the correct alignment between them can be constructed. This approach to structure prediction is possible because a small change in the protein sequence usually results in a small change in its 3D structure [7]. Although considerable progress has been made in the ab initio protein structure prediction, comparative protein structure modeling remains the most accurate prediction method. The overall accuracy of comparative models spans a wide range. At the low end of the spectrum are the low resolution models whose only essentially correct feature is their fold. At the high end of the spectrum are the models with an accuracy comparable to medium resolution crystallographic structures [6]. Even low resolution models are often useful for addressing biological questions, because function can often be predicted from only coarse structural features of a model.
