On the stability of protein–DNA complexes in molecular dynamics simulations using the CUFIX corrections

The molecular dynamics simulation using the so-called force field is a computational method to investigate the conformational stability and dynamics of various biomolecules, including proteins and nucleic acids. While a force-balanced force field is necessary for realistic simulations, recent studies revealed that all standard CHARMM and AMBER force fields over-stabilize the protein–DNA interfaces, resulting in abnormally slow diffusion of DNA-binding proteins. To address this issue, we recently developed the CUFIX corrections by calibrating the electrostatic interactions at the protein–DNA interfaces and demonstrated that the CUFIX corrections dramatically improved the diffusion dynamics of DNA-binding proteins. However, whether the improvement was achieved correctly or at the cost of abnormal destabilization of protein–DNA interactions should be validated. Here, we prove that the CUFIX corrections achieved the balance by demonstrating that the CUFIX corrections maintain the complex structure of DNA and a histone-like protein, Hbb.