High accuracy template based modeling by global optimization

• Published in: Proteins, structure, function, and bioinformatics Vol. 69; no. S8; pp. 83 - 89
• Main Authors: Joo, Keehyoung, Lee, Jinwoo, Lee, Sunjoong, Seo, Joo-Hyun, Lee, Sung Jong, Lee, Jooyoung
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2007
• Subjects: Amino Acid Sequence; Computational Biology - methods; Computer Simulation; fold recognition; global optimization; model evaluation; Models, Molecular; Molecular Sequence Data; multiple alignment; Protein Conformation; protein structure prediction; Proteins - chemistry; Sequence Alignment; side-chain modeling; TBM/HA; template-based modeling
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.21628

For high‐accuracy template‐based‐modeling of CASP7 targets, we have applied a procedure based on the rigorous optimization of score functions at three stages: multiple alignment, chain building, and side‐chain modeling. We applied the conformational space annealing method to a newly developed consistency based score function for multiple alignment. For chain building, we optimized the MODELLER energy function. For side‐chain modeling, we optimized a SCWRL‐like energy function using a rotamer library constructed specifically for a given target sequence. By rigorous optimization, we have achieved significant improvement in backbone as well as side‐chain modeling for TBM and TBM/HA targets. For most TBM/HA targets (17/26), the predicted model was more accurate than the model one can construct from the best template in a posteriori fashion. It appears that the current method can extract relevant information out of multiple templates. Proteins 2007. © 2007 Wiley‐Liss, Inc.