TASSER-Lite: an automated tool for protein comparative modeling.

This study involves the development of a rapid comparative modeling tool for homologous sequences by extension of the TASSER methodology, developed for tertiary structure prediction. This comparative modeling procedure was validated on a representative benchmark set of proteins in the Protein Data Bank composed of 901 single domain proteins (41-200 residues) having sequence identities between 35-90% with respect to the template. Using a Monte Carlo search scheme with the length of runs optimized for weakly/nonhomologous proteins, TASSER often provides appreciable improvement in structure quality over the initial template. However, on average, this requires approximately 29 h of CPU time per sequence. Since homologous proteins are unlikely to require the extent of conformational search as weakly/nonhomologous proteins, TASSER's parameters were optimized to reduce the required CPU time to approximately 17 min, while retaining TASSER's ability to improve structure quality. Using this optimized TASSER (TASSER-Lite), we find an average improvement in the aligned region of approximately 10% in root mean-square deviation from native over the initial template. Comparison of TASSER-Lite with the widely used comparative modeling tool MODELLER showed that TASSER-Lite yields final models that are closer to the native. TASSER-Lite is provided on the web at (http://cssb.biology.gatech.edu/skolnick/webservice/tasserlite/index.html).