Monte Carlo Simulation Algorithm for B-DNA

Published

September 27, 2016

Author(s)

Steven C Howell, Xiangyun Qiu, Joseph E. Curtis

Abstract

The growing interest in determining structures of macromolecules containing deoxyribonucleic acid (DNA) in solution and their structure-function relationship has encouraged experiments using methods such as solution small angle X-ray and neutron scattering (SAXS and SANS). One such DNA system of interest is the DNA-protein complex known as a nucleosome, the building block of chromatin in eukaryotic cells. For many macromolecules, including nucleosomes, a wealth of structure knowledge has been obtained using experimental techniques which examine the macromolecule in a static environment; such techniques include X-ray crystallography, atomic force microscopy, and cryo-electron microscopy. Solution SAXS and SANS provide a means to explore these microstructure. Solution SAXS and SANS provide a means to explore these macrmolecules in a more cellular-like environment but there exists a need for open source software to generate atomic structurs of DNA that subsequently allow for the comparison to experimental results. We present an algorithm which uses an all-atom model for a biological macromolecule containing DNA to rapidly generate an ensemble of atomic models, which can then be compared with experimental data. This algorithm represents user designated flexible DNA using a coarse-grained (CG) wormlike chain model, samples toresions of the CG DNA, recovers an all-atom model based on the final CG configuration, then minimization relaxes then strain created at the boundary between CG beads. Using this algorithm on commodity computing hardware, one can rapidly generate an ensemble of molecular models, with atomic detail not othwerwise available. Together with SAXS or SANS data, such an ensemble can be used to provide clear insight into experimental scattering results thereby elucidating the dynamic solution structure of DNA macromolecules. We demonstrate the ensemble results from simulations applying this algorithm to a single nucleosome and an array of four nucleosomes. Compared to currently available software resources, the modeling capability provided with this algorithm will revolutionize experiment driven modeling of macrmolecules containing DNA, particularly nuclesomes and nucleosome array. The CG Monte Carlo DNA algorithm has been implemented on a web user interface and is available for general use (https://sassie-web.chem.utk.edu/sassie2/).

Citation

Journal of Computational Chemistry

Volume

37

Pub Type

Journals

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Keywords

Molecular Monte Carlo, DNA, scattering

Citation

Howell, S. , Qiu, X. and Curtis, J. (2016), Monte Carlo Simulation Algorithm for B-DNA, Journal of Computational Chemistry, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=919478 (Accessed December 11, 2024)