Sequence Recognition Mechanism of Homeodomain Proteins Revealed by Millisecond-Long Molecular Dynamics Simulations
발표자
()
초록
내용
Biomolecules contain information that determines their structure and function. Among DNA-recognizing proteins, transcription factors play a fundamental role in gene regulation by identifying specific target sites. However, the molecular mechanisms of diffusion and sequence recognition of transcription factors remain elusive due to the dynamic nature of the problem. We will show how atomistic molecular dynamics (MD) simulations, which use carefully adjusted force field parameters, can help us understand how homeodomain proteins, a type of transcription factor, recognize sequences. Through millisecond-long MD simulations, we were able to reveal the roles of both the recognition helix binding to the major groove and the intrinsically disordered region (IDR) binding to the minor groove in sequence recognition. Our simulations offer an unprecedentedly detailed insight into the function of IDRs in the target search mechanism.