Venclovas C
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Proteins. 2001;Suppl 5:47-54. doi: 10.1002/prot.10008.
Comparative modeling aims at constructing molecular models for proteins of unknown structure, by using known structures of related proteins as templates. To test the comparative modeling approach reported here, predictions for 13 target proteins were submitted during the fourth round of "blind" protein structure prediction experiment (CASP4; http://PredictionCenter.llnl.gov/casp4). Sequence identity between these target proteins and the closest known structures ranged from 13 to 58%, indicating a broad spectrum of prediction difficulty. Although this broad difficulty range required addressing a variety of issues, the most important proved to be sequence-structure alignment for distant homology targets. The alignment step was based on structure-based evaluation of alignment variants produced mainly with PSI-BLAST intermediate sequence search procedure (PSI-BLAST-ISS). Although a fraction of correctly aligned residues in resulting models was markedly better than the average in all cases, for distant homology targets it was still considerably below the estimated achievable level. Results with CASP4 targets show that, along with the correctness of sequence-structure alignments, effective use of multiple template structures may significantly increase accuracy of the model structure. Improvement in this area should also result in more accurate loop modeling and side-chain prediction.
比较建模旨在通过使用相关蛋白质的已知结构作为模板，为未知结构的蛋白质构建分子模型。为了测试本文报道的比较建模方法，在第四届“盲法”蛋白质结构预测实验（CASP4；http://PredictionCenter.llnl.gov/casp4）的第四轮中，提交了对13个目标蛋白质的预测。这些目标蛋白质与最接近的已知结构之间的序列同一性范围为13%至58%，这表明预测难度范围很广。尽管这个广泛的难度范围需要解决各种问题，但最重要的问题被证明是远同源性目标的序列-结构比对。比对步骤基于主要通过PSI-BLAST中间序列搜索程序（PSI-BLAST-ISS）产生的比对变体的基于结构的评估。尽管在所有情况下，所得模型中正确比对残基的比例明显优于平均水平，但对于远同源性目标，该比例仍远低于估计的可达到水平。CASP4目标的结果表明，除了序列-结构比对的正确性之外，有效使用多个模板结构可能会显著提高模型结构的准确性。在这一领域的改进也应该会带来更准确的环建模和侧链预测。
