K-Nearest Neighbor and Random Forest-Based Prediction of Putative Tyrosinase Inhibitory Peptides of Abalone Haliotis diversicolor

Molecules. 2021 Jun 16;26(12):3671. doi: 10.3390/molecules26123671.


Skin pigment disorders are common cosmetic and medical problems. Many known compounds inhibit the key melanin-producing enzyme, tyrosinase, but their use is limited due to side effects. Natural-derived peptides also display tyrosinase inhibition. Abalone is a good source of peptides, and the abalone proteins have been used widely in pharmaceutical and cosmetic products, but not for melanin inhibition. This study aimed to predict putative tyrosinase inhibitory peptides (TIPs) from abalone, Haliotis diversicolor, using k-nearest neighbor (kNN) and random forest (RF) algorithms. The kNN and RF predictors were trained and tested against 133 peptides with known anti-tyrosinase properties with 97% and 99% accuracy. The kNN predictor suggested 1075 putative TIPs and six TIPs from the RF predictor. Two helical peptides were predicted by both methods and showed possible interaction with the predicted structure of mushroom tyrosinase, similar to those of the known TIPs. These two peptides had arginine and aromatic amino acids, which were common to the known TIPs, suggesting non-competitive inhibition on the tyrosinase. Therefore, the first version of the TIP predictors could suggest a reasonable number of the TIP candidates for further experiments. More experimental data will be important for improving the performance of these predictors, and they can be extended to discover more TIPs from other organisms. The confirmation of TIPs in abalone will be a new commercial opportunity for abalone farmers and industry.

Keywords: abalone; anti-tyrosinase peptides; bioinformatics; k-nearest neighbor; machine learning; random forest.

MeSH terms

  • Algorithms
  • Animals
  • Cluster Analysis
  • Computational Biology / methods
  • Gastropoda / chemistry
  • Gastropoda / metabolism*
  • Machine Learning
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism*
  • Monophenol Monooxygenase / pharmacology
  • Peptides / pharmacology


  • Peptides
  • Monophenol Monooxygenase