Structural characteristics of 2'-O-(2-methoxyethyl)-modified nucleic acids from molecular dynamics simulations

Kenneth E. Lind, Venkatraman Mohan, Muthiah Manoharan, David M. Ferguson

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27 Citations (Scopus)

Abstract

The structure and physical properties of 2'-sugar substituted O-(2-methoxyethyl) (MOE) nucleic acids have been studied using molecular dynamics simulations. Nanosecond simulations on the duplex MOE[CCAACGTTGG]-r[CCAACGUUGG] in aqueous solution have been carried out using the particle mesh Ewald method. Parameters for the simulation have been developed from ab initio calculations on dimethoxyethyl fragments in a manner consistent with the AMBER 4.1 force field database. The simulated duplex is compared with the crystal structure of the self-complementary duplex d[GCGTAT(MOE)ACGC]2, which contains a single modification in each strand. Structural details from each sequence have been analyzed to rationalize the stability imparted by substitution with 2'-O-(2-methoxyethyl) side chains. Both duplexes have an A-form structure, as indicated by several parameters, most notably a C3' endo sugar pucker in all residues. The simulated structure maintains a stable A-form geometry throughout the duration of the simulation with an average RMS deviation of 2.0 Å from the starting A-form structure. The presence of the 2' substitution appears to lock the sugars in the C3' endo conformation, causing the duplex to adopt a stable A-form geometry. The side chains themselves have a fairly rigid geometry with trans, trans, gauche+/- and trans rotations about the C2'-O2', O2'-CA', CA'-CB' and CB'-OC' bonds respectively.

Original languageEnglish (US)
Pages (from-to)3694-3699
Number of pages6
JournalNucleic acids research
Volume26
Issue number16
DOIs
StatePublished - Aug 15 1998

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Structural characteristics of 2'-O-(2-methoxyethyl)-modified nucleic acids from molecular dynamics simulations. / Lind, Kenneth E.; Mohan, Venkatraman; Manoharan, Muthiah; Ferguson, David M.

In: Nucleic acids research, Vol. 26, No. 16, 15.08.1998, p. 3694-3699.

Research output: Contribution to journalArticle

Lind, Kenneth E. ; Mohan, Venkatraman ; Manoharan, Muthiah ; Ferguson, David M. / Structural characteristics of 2'-O-(2-methoxyethyl)-modified nucleic acids from molecular dynamics simulations. In: Nucleic acids research. 1998 ; Vol. 26, No. 16. pp. 3694-3699.
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