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The lac repressor can fold a 385 bp-long DNA loop into 4 different conformations

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One of the most fascinating aspects of molecular biology is how objects of very different sizes are involved in the intricate biological machinery of living cells. A small protein may bind to DNA many times larger than itself and fold the DNA into a loop to regulate nearby genes. Understanding of such processes requires coupling of the dynamics of an individual protein to the dynamics of a long, looped DNA double helix. This can be achieved best through a so-called multi-scale approach that describes the protein motion at atomic resolution and the larger DNA in a less resolved manner as an elastic rod, i.e., a physical object behaving much like a twisted garden hose. Mathematical equations can be devised that capture the behavior of the DNA "hose" bent into a loop by a bound protein, predicting the conformation of the DNA as well as the energy that the protein has to muster to keep the DNA looped (DNA prefers energetically to be straight). A recent publication studies in detail mathematically and computationally the elastic rod model of DNA, taking for a case study the DNA loop folded by the lac repressor, a celebrated protein regulating the expression of DNA in E. coli. The study explores how physical characteristics built into the the elastic rod model influence the energy and conformation of looped DNA and describes the possible ways of coupling the looped DNA to all-atom protein simulations of the lac repressor or other regulatory proteins in order to achieve the multi-scale description of a protein-DNA complex.