Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

Casey T Andrews; Brady A Campbell; Adrian H Elcock

doi:10.1021/acs.jctc.6b00883

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Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

Journal article

Peer reviewed

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations

Casey T Andrews, Brady A Campbell and Adrian H Elcock

Journal of chemical theory and computation, Vol.13(4), pp.1794-1811

04/11/2017

DOI: 10.1021/acs.jctc.6b00883

PMCID: PMC5543776

PMID: 28288277

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http://doi.org/10.1021/acs.jctc.6b00883View

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Abstract

Given the ubiquitous nature of protein-DNA interactions, it is important to understand the interaction thermodynamics of individual amino acid side chains for DNA. One way to assess these preferences is to perform molecular dynamics (MD) simulations. Here we report MD simulations of 20 amino acid side chain analogs interacting simultaneously with both a 70-base-pair double-stranded DNA and with a 70-nucleotide single-stranded DNA. The relative preferences of the amino acid side chains for dsDNA and ssDNA match well with values deduced from crystallographic analyses of protein-DNA complexes. The estimated apparent free energies of interaction for ssDNA, on the other hand, correlate well with previous simulation values reported for interactions with isolated nucleobases, and with experimental values reported for interactions with guanosine. Comparisons of the interactions with dsDNA and ssDNA indicate that, with the exception of the positively charged side chains, all types of amino acid side chain interact more favorably with ssDNA, with intercalation of aromatic and aliphatic side chains being especially notable. Analysis of the data on a base-by-base basis indicates that positively charged side chains, as well as sodium ions, preferentially bind to cytosine in ssDNA, and that negatively charged side chains, and chloride ions, preferentially bind to guanine in ssDNA. These latter observations provide a novel explanation for the lower salt dependence of DNA duplex stability in GC-rich sequences relative to AT-rich sequences.

Thermodynamics

Salts - chemistry

Amino Acids - chemistry

DNA - chemistry

Solvents - chemistry

Molecular Dynamics Simulation

Details

Title: Subtitle: Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations
Creators: Casey T Andrews - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Brady A Campbell - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Adrian H Elcock - Department of Biochemistry, University of Iowa , Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: Journal of chemical theory and computation, Vol.13(4), pp.1794-1811
DOI: 10.1021/acs.jctc.6b00883
PMID: 28288277
PMCID: PMC5543776
NLM abbreviation: J Chem Theory Comput
ISSN: 1549-9618
eISSN: 1549-9626
Publisher: United States
Grant note: R01 GM087290 / NIGMS NIH HHS R01 GM099865 / NIGMS NIH HHS
Language: English
Date published: 04/11/2017
Academic Unit: Surgery; Physics and Astronomy; Biochemistry and Molecular Biology
Record Identifier: 9984024406902771

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