title: Interplay of Protein Binding Interactions, DNA Mechanics, and Entropy in DNA Looping Kinetics.
abstract: DNA looping plays a key role in many fundamental biological processes, including gene regulation, recombination, and chromosomal organization. The looping of DNA is often mediated by proteins whose structural features and physical interactions can alter the length scale at which the looping occurs. Looping and unlooping processes are controlled by thermodynamic contributions associated with mechanical deformation of the DNA strand and entropy arising from thermal fluctuations of the conformation. To determine how these confounding effects influence DNA looping and unlooping kinetics, we present a theoretical model that incorporates the role of the protein interactions, DNA mechanics, and conformational entropy. We show that for shorter DNA strands the interaction distance affects the transition state, resulting in a complex relationship between the looped and unlooped state lifetimes and the physical properties of the looped DNA. We explore the range of behaviors that arise with varying interaction distance and DNA length. These results demonstrate how DNA deformation and entropy dictate the scaling of the looping and unlooping kinetics versus the J-factor, establishing the connection between kinetic and equilibrium behaviors. Our results show how the twist-and-bend elasticity of the DNA chain modulates the kinetics and how the influence of the interaction distance fades away at intermediate to longer chain lengths, in agreement with previous scaling predictions.
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, California.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mulligan
authors.affiliation: Department of Physics, California Institute of Technology, Pasadena, California.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Applied Physics and Department of Biology, California Institute of Technology, Pasadena, California.
authors.forename: Rob
authors.initials: R
authors.lastname: Phillips
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, California; Biophysics Program, Stanford University, Stanford, California; Department of Materials Science and Engineering, Stanford University, Stanford, California; Department of Applied Physics, Stanford University, Stanford, California. Electronic address: ajspakow@stanford.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Spakowitz
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D004548:Elasticity; D019277:Entropy; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D013314:Stress, Mechanical
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA