MOLECULAR-DYNAMICS SIMULATION STUDY OF DNA DODECAMER D(CGCGAATTCGCG) IN SOLUTION - CONFORMATION AND HYDRATION

A molecular dynamics simulation of the dodecamer duplex d(CGCGAATTCGCG ) using the particle mesh Ewald sum assumed a B-conformation remarkabl y close to the observed X-ray structure. The Ewald summation method ef fectively eliminates the usual ''cut-off'' of long-range interactions and allowed us to evaluate the full effect of the electrostatic forces . This simulation showed remarkable agreement with the Dickerson X-ray structure in both average structure and B-factors; within the EcoRI s ite itself, the rms deviation between the average theoretical and obse rved structures was 1.1 Angstrom. The width of the minor groove fluctu ated between a wide and narrow configuration with the latter correspon ding closely to the X-ray structure. The simulation also suggested a s trong sequence-dependent signature on the minor groove width in both w ide and narrow conformers. Hydration shells in both the major and mino r grooves were observed. The ''spine of hydration'' in the minor groov e was clear. In the major groove the first hydration shell appears to be a ribbon-like structure that reproduces the principal features of o bserved X-ray structures; subtle variations of this hydration pattern suggest sequence dependencies. Sequence-dependent features were also e xamined for helical and other geometric parameters. The successful rep roduction of many experimentally observed fine structural features sho ws that the Ewald summation significantly improves the fidelity of the calculations. (C) 1997 Academic Press Limited.