Molecular dynamics simulations revealed structural differences among TTHA1873-DNA interaction

This study aims to investigate the comparative binding pattern of TTHA1873 and its mutants (R55A and R138A) with DNA through molecular docking and molecular dynamics (MD) simulations. The docking results suggests that the Wild type (WT-TTHA1873), R55A, R138A and double mutant R55A/R138A having docking scores of -225.80 kcal/mol, -209.81 kcal/mol, -197.53 kcal/mol, -195.55 kcal/mol respectively and WT-TTHA1873 has more significant binding capability with DNA in comparison to mutants. The MD analysis revealed that the WT-TTHA1873 demonstrated stable interactions with DNA and exhibited a reduced conformational space compared to the mutants. By examining the atomic interactions, it was observed that significant variations in the hydrogen bonding pattern between WT-TTHA1873 and its mutants while interacting with DNA resulted in structural anomalies in the mutants and differences in DNA-binding specificity. The calculated binding free energies imply more stability of the WT-TTHA1873-DNA complex, while the mutants showed lesser binding affinity toward its interacting partner, double-stranded DNA. It is apparent that substituting single mutation R55A and R138A on TTHA1873 abolishes their DNA-binding ability. The present study portrays the critical role of R55 and R138 from TTHA1873 as likely involved in DNA binding.