Mechanistic and structural insight into R2R3-MYB transcription factor in plants: molecular dynamics based binding free energy analysis

The MYB transcription factor (TF) family is essential for various plant growth and development processes, including responses to biotic and abiotic stresses. This study investigated the R2R3-MYB protein structure from five plants, including cereal crops. The R2R3-MYB protein structure was docked with the DNA structure, and the best complexes were selected for two runs of molecular dynamics (MD) simulations to investigate the key interacting residues and conformational changes in the R2R3-MYB proteins caused by DNA binding. The MM/PBSA method calculated the binding free energy for each R2R3-MYB protein-DNA complex, showing strong interaction. Hydrophobic and hydrogen bonds significantly stabilized the R2R3-MYB protein-DNA complexes. The principal component analysis showed high restrictions on the movement of protein atoms in the phase space. A similar MD simulation analysis was performed using the crystal structure of the R2R3-MYB protein-DNA complex from Arabidopsis thaliana, and the generated complexes resembled the X-ray crystal structure. This is the first detailed study on the R2R3-MYB protein-DNA complex in cereal crops, providing a cost-effective solution to identify the key interacting residues and analyze the conformational changes in the MYB domain before and after DNA binding.Communicated by Ramaswamy H. Sarma.