Homology modeling of proteins using multiple models and consensus sequence alignment

Homology modeling predicts the three-dimensional structure of a protein (target), given its sequence, on the basis of sequence similarity to a protein of known structure (template). The main factor determining the accuracy of the model is the alignment of template and target sequences. Two methods are described to improve the reliability of this step. First, multiple alignment are produced, converted into models, and then the structure with the lowest free energy is chosen. The method performs remarkably well for targets for which a good template is available. In the second approach, the alignment is based on the consensus of five popular methods. It provides reliable prediction of the structurally conserved framework region, but the alignment length is reduced. A homology modeling tool combining the two methods is in preparation.