Biomedical subjects

D Flatters

Publications and source records attributed to D Flatters.

3 recordsLinked to original sources

PubMed1999

From atomic to mesoscopic descriptions of the internal dynamics of DNA.

An analysis of four 1-ns molecular dynamics trajectories for two different 15-bp oligonucleotides is presented. Our aim is to show which groups of atoms can be treated as rigid bodies within a bead representation of DNA, independently of the base sequence and for any conformations belonging to the A/B family. Five models with moderate intragroup deformations are proposed in which the groups are formed of atoms belonging to a single nucleotide or to a complementary nucleotide pair. The influence of group deformation in two of these models is studied using canonical correlation analysis, and it is shown that the internal DNA dynamics is indeed dominated by the rigid motion of the defined atom groups. Finally, using one of the models within a bead representation of duplex DNA makes it possible to obtain stretching, torsional, and bending rigidities in reasonable agreement with experiment but points to strongly correlated stretching motions.

Base Sequence↗

PubMed1998

Sequence-dependent dynamics of TATA-Box binding sites.

We have carried out two nanosecond-length molecular dynamics simulations on a DNA oligomer, d(GCGTAAAAAAAACGC)2, which contains a weak binding site for the TATA-box binding protein. An analysis of the resulting trajectories shows that this oligomer behaves differently from a related oligomer [d(GCGTATATAAAACGC)2] studied earlier using the same protocol (Flatters, D., M. Young, D. L. Beveridge, and R. Lavery. 1997. Conformational properties of the TATA-box binding sequence of DNA. J. Biomol. Struct. & Dyn. 14:757-765), and which contains a strong binding site for the same protein. The two basepair mutations that relate these oligomers lead to significant changes in time-averaged structure and in dynamic behavior, which extend over entire length of the oligomer and appear to be compatible with the experimentally observed decrease of binding and functional activity. These results suggest that molecular dynamics simulations, taking into account explicit solvent and counterions, and avoiding the truncation of electrostatic interactions, are a powerful tool for investigating the indirect aspects of protein-nucleic acid recognition.

Base Sequence↗

PubMed1997

Conformational properties of the TATA-box binding sequence of DNA.

Nanosecond scale molecular dynamics simulations in water demonstrate that the DNA oligomer, GCGTATATAAAACGC, which contains a target site for the TATA-box binding protein (TBP), has an intrinsic preference to adopt an A-like conformation in the region of the TATA-box and undergoes bending related to that seen within in the TBP complex. This result is obtained from two independent simulations using different starting structures. In line with earlier suggestions of Guzikevich-Guerstein and Shakked, these simulations imply that an A-DNA conformation may be an important intermediate step in forming the strongly distorted DNA observed within the crystallographically determined complex with TBP. These results also support modeling studies by Lebrun et al. which suggest that the TBP binding mechanism can be broken down into a backbone transition to an A-like form coupled with a mechanical distortion which locally stretches and unwinds the DNA.

Binding Sites↗