Fully solvated molecular dynamics simulations of duplexes formed by modified oligonucleotides with xylo/phosphodiesteric and xylo/phosphonate internucleoside linkages and their natural counterpart

• Published in: Computer physics communications Vol. 147; no. 1; pp. 158 - 161
• Main Authors: Barvı́k, Ivan, Štěpánek, Josef, Bok, Jiřı́
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2002; Elsevier Science
• Subjects: AMBER; Antisense DNA; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; General aspects; MD simulations; Molecular biophysics; mRNA; PME; Structure and bonding; Theory and modeling; computer simulation; MD simulations; PME; mRNA; Antisense DNA; AMBER; Numerical simulation; Oligonucleotide; Solvation; Molecular dynamics method; Conformation
• ISSN: 0010-4655; 1879-2944
• DOI: 10.1016/S0010-4655(02)00236-9

The impact of the xylo/phosphodiesteric and xylo/phosphonate internucleoside linkage modification on the ability of the modified oligonucleotide to hybridize with a natural DNA strand was studied by fully solvated molecular dynamics (MD) simulations. Three undecamer complexes were analyzed: natural dT 11.dA 11 duplex as a reference and two of its analogs with modified linkages in the deoxyadenosine chain. The modified linkages were of the 5′OPO 2O 3 ′XYLO (A X ) or 5′OPO 2 CH 2 O 3 ′XYLO (A CX) type. Simulations were performed by using the AMBER 5.0 software package with the force field completed by a set of parameters needed to model the modified segments of the A CX oligonucleotide. Both modifications were found to lead to stable double helical complexes at 300 K.