Integration of Machine Learning and Structural Analysis for Predicting Peptide Antibiofilm Effects: Advancements in Drug Discovery for Biofilm-Related Infections.

BACKGROUND: The rise of antibiotic resistance has become a major concern, signaling the end of the golden age of antibiotics. Bacterial biofilms, which exhibit high resistance to antibiotics, significantly contribute to the emergence of antibiotic resistance. Therefore, there is an urgent need to discover new therapeutic agents with specific characteristics to effectively combat biofilm-related infections. Studies have shown the promising potential of peptides as antimicrobial agents.

OBJECTIVES: This study aimed to establish a cost-effective and streamlined computational method for predicting the antibiofilm effects of peptides. This method can assist in addressing the intricate challenge of designing peptides with strong antibiofilm properties, a task that can be both challenging and costly.

METHODS: A positive library, consisting of peptide sequences with antibiofilm activity exceeding 50%, was assembled, along with a negative library containing quorum-sensing peptides. For each peptide sequence, feature vectors were calculated, while considering the primary structure, the order of amino acids, their physicochemical properties, and their distributions. Multiple supervised learning algorithms were used to classify peptides with significant antibiofilm effects for subsequent experimental evaluations.

RESULTS: The computational approach exhibited high accuracy in predicting the antibiofilm effects of peptides, with accuracy, precision, Matthew's correlation coefficient (MCC), and F1 score of 99%, 99%, 0.97, and 0.99, respectively. The performance level of this computational approach was comparable to that of previous methods. This study introduced a novel approach by combining the feature space with high antibiofilm activity.

CONCLUSIONS: In this study, a reliable and cost-effective method was developed for predicting the antibiofilm effects of peptides using a computational approach. This approach allows for the identification of peptide sequences with substantial antibiofilm activities for further experimental investigations. Accessible source codes and raw data of this study can be found online (hiABF), providing easy access and enabling future updates.