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PMID: 9370428 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A 5-nanosecond molecular dynamics trajectory for B-DNA: analysis of structure, motions, and solvation.

Biophysical journal ·Vol. 73 ·No. 5 ·1997-11-00 ·Pages 2313-36

Young MA, Ravishanker G, Beveridge DL

Abstract

We report the results of four new molecular dynamics (MD) simulations on the DNA duplex of sequence d(CGCGAATTCGCG)2, including explicit consideration of solvent water, and a sufficient number of Na+ counterions to provide electroneutrality to the system. Our simulations are configured particularly to characterize the latest MD models of DNA, and to provide a basis for examining the sensitivity of MD results to the treatment of boundary conditions, electrostatics, initial placement of solvent, and run lengths. The trajectories employ the AMBER 4.1 force field. The simulations use particle mesh Ewald summation for boundary conditions, and range in length from 500 ps to 5.0 ns. Analysis of the results is carried out by means of time series for conformationalm, helicoidal parameters, newly developed indices of DNA axis bending, and groove widths. The results support a dynamically stable model of B-DNA for d(CGCGAATTCGCG)2 over the entire length of the trajectory. The MD results are compared with corresponding crystallographic and NMR studies on the d(CGCGAATTCGCG)2 duplex, and placed in the context of observed behavior of B-DNA by comparisons with the complete crystallographic data base of B-form structures. The calculated distributions of mobile solvent molecules, both water and counterions, are displayed. The calculated solvent structure of the primary solvation shell is compared with the location of ordered solvent positions in the corresponding crystal structure. The results indicate that ordered solvent positions in crystals are roughly twice as structured as bulk water. Detailed analysis of the solvent dynamics reveals evidence of the incorporation of ions in the primary solvation of the minor groove B-form DNA. The idea of localized complexation of otherwise mobile counterions in electronegative pockets in the grooves of DNA helices introduces an additional source of sequence-dependent effects on local conformational, helicoidal, and morphological structure, and may have important implications for understanding the functional energetics and specificity of the interactions of DNA and RNA with regulatory proteins, pharmaceutical agents, and other ligands.

MeSH Terms
Computer Simulation Crystallography, X-Ray DNA/chemistry Models, Molecular Nucleic Acid Conformation Oligodeoxyribonucleotides/chemistry Sodium/chemistry Water/metabolism
Chemicals
Oligodeoxyribonucleotides Water DNA Sodium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Young M A
Chemistry Department, Wesleyan University, Middletown, Connecticut 06459, USA.
Ravishanker G
Beveridge D L
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(97)78263-8
Published
1997-11-00
Pages
2313-36
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1181136
Subset
IM
Grants
NIGMS NIH HHS · GM-08271 · United States
NIGMS NIH HHS · GM-37909 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(97)78263-8 PMC Full Text View journal details
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