Marti-Renom Marc A, Madhusudhan M S, Sali Andrej
Mission Bay Genentech Hall, University of California, San Francisco, San Francisco, CA 94143, USA.
Protein Sci. 2004 Apr;13(4):1071-87. doi: 10.1110/ps.03379804.
The accuracy of an alignment between two protein sequences can be improved by including other detectably related sequences in the comparison. We optimize and benchmark such an approach that relies on aligning two multiple sequence alignments, each one including one of the two protein sequences. Thirteen different protocols for creating and comparing profiles corresponding to the multiple sequence alignments are implemented in the SALIGN command of MODELLER. A test set of 200 pairwise, structure-based alignments with sequence identities below 40% is used to benchmark the 13 protocols as well as a number of previously described sequence alignment methods, including heuristic pairwise sequence alignment by BLAST, pairwise sequence alignment by global dynamic programming with an affine gap penalty function by the ALIGN command of MODELLER, sequence-profile alignment by PSI-BLAST, Hidden Markov Model methods implemented in SAM and LOBSTER, pairwise sequence alignment relying on predicted local structure by SEA, and multiple sequence alignment by CLUSTALW and COMPASS. The alignment accuracies of the best new protocols were significantly better than those of the other tested methods. For example, the fraction of the correctly aligned residues relative to the structure-based alignment by the best protocol is 56%, which can be compared with the accuracies of 26%, 42%, 43%, 48%, 50%, 49%, 43%, and 43% for the other methods, respectively. The new method is currently applied to large-scale comparative protein structure modeling of all known sequences.
通过在比较中纳入其他可检测到的相关序列，可以提高两个蛋白质序列之间比对的准确性。我们优化并基准测试了这样一种方法，该方法依赖于比对两个多序列比对，每个多序列比对包含两个蛋白质序列中的一个。MODELLER的SALIGN命令中实现了13种不同的用于创建和比较与多序列比对相对应的图谱的协议。使用一组由200个基于结构的成对比对组成的测试集（序列同一性低于40%）来基准测试这13种协议以及一些先前描述的序列比对方法，包括BLAST的启发式成对序列比对、MODELLER的ALIGN命令使用仿射空位罚分函数通过全局动态规划进行的成对序列比对、PSI-BLAST的序列-图谱比对、SAM和LOBSTER中实现的隐马尔可夫模型方法、SEA依赖预测局部结构的成对序列比对以及CLUSTALW和COMPASS的多序列比对。最佳新协议的比对准确性明显优于其他测试方法。例如，最佳协议相对于基于结构的比对正确比对残基的比例为56%，而其他方法的准确性分别为26%、42%、43%、48%、50%、49%、43%和43%。该新方法目前应用于所有已知序列的大规模比较蛋白质结构建模。
