Book of Abstracts: Albany 2003
June 17-21 2003
Molecular Dynamics Simulations of Papilloma Virus E2 DNA Sequences: Dynamical Models for Oligonucleotide Structures in Solution
The specificity of Papilloma virus E2 protein-DNA binding depends critically upon the sequence of a region of the DNA not in direct contact with the protein and, one of the simplest known examples of indirect readout. In the crystalline state, the E2 DNA oligonucleotide sequence, d(ACCGAATTCGGT), exhibits three different structural forms. We report the studies of the structure of E2 DNA in solution based on molecular dynamics simulations including counterions and water. The simulations were carried out using the AMBER suite of programs and the parm94 force field, utilizing both the canonical and various crystallographic structures as initial points of departure. In 4 nanosecond trajectories, all MDs converged on a single dynamical structure of d(ACCGAATTCGGT) in solution. The predicted structure is in close accord with two of the three crystal molecules, and indicates that a significant kink in the double helix at the central ApT step in the other crystal molecule may be a packing effect. In order to study the role of structural adaptation of the DNA in the binding process, a simulation on the 16-mer cognate sequence d(CAACCGAATTCGGTTG) was initiated from the crystallographic coordinates taken from the protein DNA complex. MD simulations relaxed rapidly back to the dynamical structure predicted from the previous simulations. The MD results show that the bound form E2 DNA is a dynamically unstable structure in the absence of protein, and arises as a consequence of both structural changes intrinsic to the sequence and induced by the interaction with protein.
K. Suzie Byun
Department of Chemistry