Sequence alignment using machine learning for accurate template-based protein structure prediction

MotivationTemplate-based modeling, the process of predicting the tertiary structure of a protein by using homologous protein structures, is useful if good templates can be found. Although modern homology detection methods can find remote homologs with high sensitivity, the accuracy of template-based models generated from homology-detection-based alignments is often lower than that from ideal alignments.\n\nResultIn this study, we propose a new method that generates pairwise sequence alignments for more accurate template-based modeling. The proposed method trains a machine learning model using the structural alignment of known homologs. It is difficult to directly predict sequence alignments using machine learning. Thus, when calculating sequence alignments, instead of a fixed substitution matrix, this method dynamically predicts a substitution score from the trained model. We evaluate our method by carefully splitting the training and test datasets and comparing the predicted structures accuracy with that of state-of-the-art methods. Our method generates more accurate tertiary structure models than those produced from alignments obtained by other methods.\n\nAvailability and Implementationhttps://github.com/shuichiro-makigaki/exmachina\n\nContactishida@c.titech.ac.jp or makigaki@cb.cs.titech.ac.jp