Background: Protein chains are generally long and consist of multiple domains. Domains are distinct structural units of a protein that can evolve and function independently. The accurate prediction of protein domain linkers and boundaries is often regarded as the initial step of protein tertiary structure and function predictions. Such information not only enhances protein-targeted drug development but also reduces the experimental cost of protein analysis by allowing researchers to work on a set of smaller and independent units. In this study, we propose a novel and accurate domain-linker prediction approach based on protein primary structure information only. We utilize a nature-inspired machine-learning model called Random Forest along with a novel domain-linker profile that contains physiochemical and domain-linker information of amino acid sequences.
Results: The proposed approach was tested on two well-known benchmark protein datasets and achieved 68% sensitivity and 99% precision, which is better than any existing protein domain-linker predictor. Without applying any data balancing technique such as class weighting and data re-sampling, the proposed approach is able to accurately classify inter-domain linkers from highly imbalanced datasets.
Conclusion: Our experimental results prove that the proposed approach is useful for domain-linker identification in highly imbalanced single- and multi-domain proteins.