TY - JOUR
T1 - Probing the role of structural water in a duplex oligodeoxyribonucleotide containing a water-mimicking base analog
AU - Kosztin, Dorina
AU - Gumport, Richard I.
AU - Schulten, Klaus
N1 - Funding Information:
We would like to thank Jason Rockhill for helpful discussions and a critical reading of the manuscript and R. Brunner and J. Phillips for help with NAMD. We also thank J. Carey, Princeton University, for helpful comments. This work was supported by grants from the National Institutes of Health (PHS 5 P41 RR05969-04), the National Science Foundation (BIR-9318159, BIR 94-23827 EQ), the MCA 93S028P computer-time grant at Pittsburgh Supercomputing Center and the Roy J. Carver Charitable Trust. The figures in this paper were created with the molecular graphics program VMD (61) (http://www. ks.uiuc.edu/Research/VMD ).
PY - 1999/9/1
Y1 - 1999/9/1
N2 - Molecular dynamics simulations were performed on models of the dodecamer DNA double-stranded segment, [d(CGCGAATTCGCG)]2, in which each of the adenine residues, individually or jointly, was replaced by the water-mimicking analog 2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine (hm7c7dA). The simulations, when compared with those of the dodecamer itself, show that incorporation of the analog affects neither the overall DNA structure nor its hydrogen-bonding and stacking interactions when it replaces a single individual base. Furthermore, the water molecules near the bases in the singly-substituted oligonucleotides are similarly unaffected. Double substitutions lead to differences in all the aforementioned parameters with respect to the reference sequence. The results suggest that the analog provides a good mimic of specific 'ordered' water molecules observed in contact with DNA itself and at the interface between protein and DNA in specific complexes.
AB - Molecular dynamics simulations were performed on models of the dodecamer DNA double-stranded segment, [d(CGCGAATTCGCG)]2, in which each of the adenine residues, individually or jointly, was replaced by the water-mimicking analog 2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine (hm7c7dA). The simulations, when compared with those of the dodecamer itself, show that incorporation of the analog affects neither the overall DNA structure nor its hydrogen-bonding and stacking interactions when it replaces a single individual base. Furthermore, the water molecules near the bases in the singly-substituted oligonucleotides are similarly unaffected. Double substitutions lead to differences in all the aforementioned parameters with respect to the reference sequence. The results suggest that the analog provides a good mimic of specific 'ordered' water molecules observed in contact with DNA itself and at the interface between protein and DNA in specific complexes.
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U2 - 10.1093/nar/27.17.3550
DO - 10.1093/nar/27.17.3550
M3 - Article
C2 - 10446246
AN - SCOPUS:0033199523
SN - 0305-1048
VL - 27
SP - 3550
EP - 3556
JO - Nucleic acids research
JF - Nucleic acids research
IS - 17
ER -