Atomistic Molecular Dynamics Simulations of DNA Minicircle Topoisomers - A Practical Guide to Setup, Performance and Analysis

Aug 31, 2026

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DNA supercoiling is a common biological phenomenon, yet closed-topology constraints make supercoiled DNA harder to study experimentally than linear sequences. DNA minicircles provide a controllable closed circular model with 60–500 base pairs, enabling biochemical investigation of supercoiled DNA mechanics. The guide delivers detailed in silico protocols to construct minicircle models, run atomistic molecular dynamics simulations, and analyze the resulting data. It also addresses computational challenges from large system sizes and highlights how parallel computing and improved experimental resolution (e.g., AFM, cryo-EM) enable better conformational sampling and timescales.

LanguageEnglish

CategoryGeneral

FormatDOCX

Pages32

Reading Time11 min

AccessFree to download

Introduction

DNA supercoiling and minicircle relevance

Model construction

Building closed-topology DNA minicircles in silico

Atomistic MD simulation setup

Preparing simulation systems and parameters

Performance considerations

Managing large system sizes and parallel computing

Analysis of simulation results

Extracting structural and mechanical insights

Outlook

Linking simulations with AFM and cryo-EM resolution

Atomistic Molecular Dynamics Simulations of DNA Minicircle Topoisomers: A Practical Guide to Setup, Performance and Analysis Thana Sutthibutpong1, Agnes Noy2 and Sarah Harris2,3 1. King Mongkut University of Technology Thonburi, 126 Pracha Uthit Road, Thun Khru, Bangkok, Thailand, 10140. 2. School of Physics and Astronomy, University of Leeds, Leeds, UK, LS2 9JT. 3. Astbury Centre for Structural and Molecular Biology, University of Leeds, Leeds, UK, LS2 9JT. Summary While DNA supercoiling is ubiquitous in vivo, the structure of supercoiled DNA is more challenging to study experimentally than simple linear sequences because the DNA must have a closed topology in order to sustain superhelical stress. DNA minicircles, which are closed circular double stranded DNA sequences typically containing between 60 and 500 base pairs, have proven to be useful biochemical tools for the study of the mechanics of supercoiled DNA. We present detailed protocols for constructing models of DNA minicircles in silico, for performing atomistic molecular dynamics (MD) simulations of supercoiled minicircle DNA and for analysing the results of the calculations. These simulations are computationally challenging due to the large system sizes. However, improvements in parallel computing software and hardware promise access to improve conformational sampling and simulation timescales. Given the concurrent improvements in the resolution of experimental techniques such as atomic force microscopy (AFM) and cryo-electron microscopy, the study of DNA minicircles will provide a more complete understanding of both the structure and the mechanics of supercoiled DNA. Key words: Atomistic molecular dynamics, DNA supercoiling 1. Introduction DNA supercoiling is ubiquitous in vivo, and is implicated in both genome organisation and gene regulation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Bates", "given" : "A. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maxwell", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "2", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "number-of-pages" : "217", "publisher" : "Oxford University Press", "title" : "DNA Topology", "type" : "book" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=e1c360c1-b146-4b89-97b9-131d3d985458" ] } ], "mendeley" : { "formattedCitation" : "(1)", "plainTextFormattedCitation" : "(1)", "previouslyFormattedCitation" : "(1)" }, "properties" : { "noteIndex" : 0 }, "schema" : "https://github.com/citation-style-language/schema/raw/master/csl-citation.json" }(1). DNA packaging in both prokaryotic and eukaryotic chromosomes can be investigated by HiC experiments, which detect spatial proximity between pairs of genomic loci through chemical cross-linking ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg3454", "ISBN" : "1471-0064 (Electronic) 1471-0056 (Linking)", "ISSN" : "1471-0064", "PMID" : "23657480", "abstract" : "How DNA is organized in three dimensions inside the cell nucleus and how this affects the ways in which cells access, read and interpret genetic information are among the longest standing questions in cell biology. Using newly developed molecular, genomic and computational approaches based on the chromosome conformation capture technology (such as 3C, 4C, 5C and Hi-C), the spatial organization of genomes is being explored at unprecedented resolution. Interpreting the increasingly large chromatin interaction data sets is now posing novel challenges. Here we describe several types of statistical and computational approaches that have recently been developed to analyse chromatin interaction data.", "author" : [ { "dropping-particle" : "", "family" : "Dekker", "given" : "Job", "non-dropping-particle" : "", "

FAQs

Why are DNA minicircle topoisomers useful for studying DNA supercoiling mechanics?

DNA minicircles are closed circular double-stranded DNA with a tractable size range (about 60–500 base pairs), providing a closed topology that sustains superhelical stress while remaining amenable to controlled modeling and biochemical study.

What core workflows does the practical guide cover?

It provides protocols for constructing DNA minicircle models in silico, performing atomistic molecular dynamics simulations of supercoiled minicircle DNA, and analyzing simulation results.

What makes atomistic MD simulations of DNA minicircles computationally challenging, and how is this addressed?

The simulations involve large system sizes, which increases computational cost and can limit conformational sampling. Improvements in parallel computing software and hardware are expected to improve sampling and accessible timescales.

Aug 31, 2026

Upload by Finn