Unveiling Switching Function of Amino Acids in Proteins Using a Machine Learning Approach

Dynamics of individual amino acids play key roles in the overall properties of proteins. However, the knowledge of protein structural features at the residue level is limited due to the current resolutions of experimental and computational techniques. To address this issue, we designed a novel machine-learning (ML) framework that uses Molecular Dynamics (MD) trajectories to identify the major conformational states of individual amino acids, classify amino acids switching between two distinct modes, and evaluate their degree of dynamic stability. The Random Forest model achieved 96.94% classification accuracy in identifying switch residues within proteins. Additionally, our framework distinguishes between the stable switch (SS) residues, which remain stable in one angular state and jump once to another state during protein dynamics, and unstable switch (US) residues, which constantly fluctuate between the two angular states. This study also illustrates the correlation between the dynamics of SS residues and the protein’s global properties.