Protein structure prediction provides valuable insights into function, and comparative modeling is one of the most reliable methods to predict 3D structures directly from amino acid sequences. However, critical problems arise during the selection of the correct templates and the alignment of query sequences therewith. We have developed an automatic protein structure prediction server, (PS) ² , which uses an effective consensus strategy both in template selection, which combines PSI-BLAST and IMPALA, and target–template alignment integrating PSI-BLAST, IMPALA and T-Coffee. (PS) ² was evaluated for 47 comparative modeling targets in CASP6 (Critical Assessment of Techniques for Protein Structure Prediction). For the benchmark dataset, the predictive performance of (PS) ² , based on the mean GTD_TS score, was superior to 10 other automatic servers. Our method is based solely on the consensus sequence and thus is considerably faster than other methods that rely on the additional structural consensus of templates. Our results show that (PS) ² , coupled with suitable consensus strategies and a new similarity score, can significantly improve structure prediction. Our approach should be useful in structure prediction and modeling. The (PS) ² is available through the website at http://ps2.life.nctu.edu.tw/ .