The wormlike chain (WLC) model of DNA bending accurately reproduces single-molecule force-extension profiles of long (kilobase) chains. These bending statistics over large scales do not, however, establish a unique microscopic model for elasticity at the 1-10 bp scale, which holds particular interest in biological contexts. Here we examine a specific microscopic description, introduced by Yan and Marko, which allows for disruption of base pairing (i.e., "melting" ) and consequently enhanced local flexibility. We first reformulate this model to ensure consistency with the well-established thermodynamics of melting in long chains. Using  Monte Carlo simulations, we compute cyclization rates of such a meltable wormlike chain (MWLC) over a broad range of chain lengths, including very short molecules (30 bp) that have not yet been explored experimentally. For chains longer than about 120 bp, including most molecules studied to date in the laboratory, we find that melting excitations have little impact on cyclization kinetics. Strong signatures of melting, which might be resolved within typical experimental scatter, emerge only for shorter chains.
The wormlike chain (WLC) model of DNA bending accurately reproduces single-molecule force-extension profiles of long (kilobase) chains. These bending statistics over large scales do not, however, establish a unique microscopic model for elasticity at the 1-10 bp scale, which holds particular interest in biological contexts. Here we examine a class of microscopic models which allow for disruption of base pairing (i.e., a `melt' or `kink', generically an `excitation' ) and consequently enhanced local flexibility. We first analyze the effect on the excitation free energy of integrating out the spatial degrees of freedom in a wormlike chain. Based on this analysis, we present a formulation of these models that ensures consistency with the well-established thermodynamics of melting in long chains. Using a new method to calculate cyclization statistics of short chains from enhanced-sampling Monte Carlo simulations, we compute J-factors of a meltable wormlike chain (MWLC) over a broad range of chain lengths, including very short molecules (30 bp) that have not yet been explored experimentally. For chains longer than about 120 bp, including most molecules studied to date in the laboratory, we find that melting excitations have little impact on cyclization kinetics. Strong signatures of melting, which might be resolved within typical experimental scatter, emerge only for shorter chains.
R
specific microscopic description, introduced by Yan and Marko, which allows
class of microscopic models which allow
R
"melting"
a `melt' or `kink', generically an `excitation'
R
reformulate this model to ensure
analyze the effect on the excitation free energy of integrating out the spatial degrees of freedom in a wormlike chain. Based on this analysis, we present a formulation of these models that ensures
A
a new method to calculate cyclization statistics of short chains from enhanced-sampling
R
cyclization rates of such
J-factors of