Transcription-factor binding and sliding on DNA studied using micro- and macroscopic models

Transcription factors (TFs) are the major regulators of gene expression. We have used a combination of computer simulations and theoretical methods to explore the atomic details for how a model TF, the lac repressor, moves on DNA in search for its specific binding site. We find that it slides along the DNA along a helical path, which allows it to probe for specific binding in a major groove. The uniqueness in the study lies in that the fully atomistic molecular dynamics model allows us to estimate the microscopic interaction energies from the TF-DNA structure and that we have developed a theoretical tool to derive macroscopic, experimentally testable, predictions for DNA residence time and sliding lengths from the microscopic interaction energies.