Sequence affects the cyclization of DNA minicircles

Q Wang, BM Pettitt - The journal of physical chemistry letters, 2016 - ACS Publications
The journal of physical chemistry letters, 2016ACS Publications
Understanding how the sequence of a DNA molecule affects its dynamic properties is a
central problem affecting biochemistry and biotechnology. The process of cyclizing short
DNA, as a critical step in molecular cloning, lacks a comprehensive picture of the kinetic
process containing sequence information. We have elucidated this process by using coarse-
grained simulations, enhanced sampling methods, and recent theoretical advances. We are
able to identify the types and positions of structural defects during the looping process at a …
Understanding how the sequence of a DNA molecule affects its dynamic properties is a central problem affecting biochemistry and biotechnology. The process of cyclizing short DNA, as a critical step in molecular cloning, lacks a comprehensive picture of the kinetic process containing sequence information. We have elucidated this process by using coarse-grained simulations, enhanced sampling methods, and recent theoretical advances. We are able to identify the types and positions of structural defects during the looping process at a base-pair level. Correlations along a DNA molecule dictate critical sequence positions that can affect the looping rate. Structural defects change the bending elasticity of the DNA molecule from a harmonic to subharmonic potential with respect to bending angles. We explore the subelastic chain as a possible model in loop formation kinetics. A sequence-dependent model is developed to qualitatively predict the relative loop formation time as a function of DNA sequence.
ACS Publications
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