Joo Keehyoung, Lee Jinwoo, Lee Sunjoong, Seo Joo-Hyun, Lee Sung Jong, Lee Jooyoung
School of Computational Sciences, Korea Institute for Advanced Study, Seoul, Korea.
Proteins. 2007;69 Suppl 8:83-9. 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.
为了对CASP7目标进行高精度的基于模板的建模，我们应用了一种基于在三个阶段对评分函数进行严格优化的程序：多序列比对、链构建和侧链建模。我们将构象空间退火方法应用于新开发的基于一致性的多序列比对评分函数。对于链构建，我们优化了MODELLER能量函数。对于侧链建模，我们使用专门为给定目标序列构建的旋转异构体库优化了类似SCWRL的能量函数。通过严格优化，我们在TBM和TBM/HA目标的主链以及侧链建模方面取得了显著改进。对于大多数TBM/HA目标（17/26），预测模型比人们可以事后从最佳模板构建的模型更准确。看来当前方法可以从多个模板中提取相关信息。
