Change in specific interactions between lactose repressor protein and DNA induced by ligand binding: molecular dynamics and molecular orbital calculations

<div><p>Lactose repressor protein (LacR) plays an essential role in controlling the transcription mechanism of genomic information from DNA to mRNA. It has been elucidated that a ligand binding to LacR regulates allosterically the specific interactions between LacR and operator DNA. However, the effect of the ligand binding on the specific interactions has not been clarified at an atomic level. In this study, we performed classical molecular dynamics (MD) and <i>ab initio</i> fragment molecular orbital simulations to elucidate the effect of ligand binding at atomic and electronic levels. The MD simulations for the solvated complexes with LacR-dimer, DNA and ligand demonstrate that the binding of an inducer IPTG to LacR-dimer significantly changes the structure of LacR-monomer to cause strong interactions between LacR-monomers, resulting in weakening the interactions between LacR-dimer and DNA. In contrast, the binding of an anti-inducer ONPF to LacR-dimer was found to enhance the interactions between LacR-dimer and DNA. These findings are consistent with the functions of IPTG and ONPF as an inducer and an anti-inducer, respectively. We therefore proposed a simplified model for the effect of the ligand binding on the specific interactions between LacR-dimer and DNA.</p>