Modeling the relaxation of internal DNA segments during genome mapping in nanochannels.

Biomicrofluidics

Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities, 421 Washington Ave. SE, Minneapolis, Minnesota 55455, USA.

Published: September 2016

We have developed a multi-scale model describing the dynamics of internal segments of DNA in nanochannels used for genome mapping. In addition to the channel geometry, the model takes as its inputs the DNA properties in free solution (persistence length, effective width, molecular weight, and segmental hydrodynamic radius) and buffer properties (temperature and viscosity). Using pruned-enriched Rosenbluth simulations of a discrete wormlike chain model with circa 10 base pair resolution and a numerical solution for the hydrodynamic interactions in confinement, we convert these experimentally available inputs into the necessary parameters for a one-dimensional, Rouse-like model of the confined chain. The resulting coarse-grained model resolves the DNA at a length scale of approximately 6 kilobase pairs in the absence of any global hairpin folds, and is readily studied using a normal-mode analysis or Brownian dynamics simulations. The Rouse-like model successfully reproduces both the trends and order of magnitude of the relaxation time of the distance between labeled segments of DNA obtained in experiments. The model also provides insights that are not readily accessible from experiments, such as the role of the molecular weight of the DNA and location of the labeled segments that impact the statistical models used to construct genome maps from data acquired in nanochannels. The multi-scale approach used here, while focused towards a technologically relevant scenario, is readily adapted to other channel sizes and polymers.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065570PMC
http://dx.doi.org/10.1063/1.4964927DOI Listing

Publication Analysis

Top Keywords

genome mapping
8
segments dna
8
molecular weight
8
rouse-like model
8
labeled segments
8
model
7
dna
6
modeling relaxation
4
relaxation internal
4
internal dna
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!