Sequence Affects the Cyclization of DNA Minicircles

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• 作者：Qian Wang ; B. Montgomery Pettitt
• 刊名：The Journal of Physical Chemistry Letters
• 出版年：2016
• 出版时间：March 17, 2016
• 年：2016
• 卷：7
• 期：6
• 页码：1042-1046
• 全文大小：373K
• ISSN：1948-7185

文摘

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.