Abstract
The ability to capture the relationship between similarity and functionality would enable the predictive design of peptide sequences for a wide range of implementations from developing new drugs to molecular scaffolds in tissue engineering and biomolecular building blocks in nanobiotechnology. Similarity matrices are widely used for detecting sequence homology but depend on the assumption that amino acid mutational frequencies reflected by each matrix are relevant to the system in which they are applied. Increasingly, neural networks and other statistical learning models solve problems related to functional prediction but avoid using known features to circumvent unconscious bias. We demonstrated an iterative alignment method that enhances predictive power of similarity matrices based a similarity metric, the Total Similarity Score. A generalized method is provided for application to amino acid sequences from inorganic and organic systems by benchmarking it on the debut quartz-binder set and 3 peptide-protein sets from the Immune Epitope Database. Pearson and Spearman Rank Correlations show that by treating the gapless Total Similarity Score as a predictor of relative binding affinity, prediction of test data has a 0.5-0.7 Pearson and Spearman Rank correlation. with respect to size of dataset. Since the benchmarks used herein are from a solid-binding peptide and a protein-peptide system, our proposed method could prove to be a highly effective general approach for establishing the predictive sequence-function relationships of among the peptides with different sequences and lengths in a wide range of biotechnology, nanomedicine and bioinformatics applications.