Model building by comparison at CASP3: Using expert knowledge and computerautomation

Ten models were constructed for the comparative modeling section of the Cri tical Assessment of Techniques for Protein Structure Prediction-3 (CASP3). Sequence identity between each target and the best possible parent(s) range d between 12% and 64%. The modeling protocol is a mixture of automated comp uter algorithms with human intervention at certain critical stages, In part icular, intervention is required to check sequence alignments and the selec tion of parameters for various computer programs. Seven of the targets were constructed from single-parent templates, and three were constructed from multiple parents, The reasons for such a high ratio of modeling from single parents only are discussed. Models constructed from multiple parents were found to be more accurate than models constructed from single parents only. A novel loop-modeling algorithm is presented that consists of fragment dat abase searches, several fragment libraries, and mean-field calculations on representative fragment candidates. (C) 1999 Wiley-Liss, Inc.