In this work, we develop a method called FTCOM for assessing the global quality of protein structural models for targets of medium and hard difficulty (remote homology) produced by structure prediction approaches such as threading or ab initio structure prediction. FTCOM requires the Cα coordinates of full length models and assesses model quality based on fragment comparison and a score derived from comparison of the model to top threading templates. On a set of 361 medium/hard targets, FTCOM was applied to and assessed for its ability to improve upon the results from the SP3, SPARKS, PROSPECTOR_3, and PRO-SP3-TASSER threading algorithms. The average TM-score improves by 5%–10% for the first selected model by the new method over models obtained by the original selection procedure in the respective threading methods. Moreover the number of foldable targets (TM-score ≥0.4) increases from least 7.6% for SP3 to 54% for SPARKS. Thus, FTCOM is a promising approach to template selection.
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