Indirect readout in drug-DNA recognition: role of sequence-dependent DNA conformation.

ABSTRACT: DNA-binding drugs have numerous applications in the engineered gene regulation. However, the drug-DNA recognition mechanism is poorly understood. Drugs can recognize specific DNA sequences not only through direct contacts but also indirectly through sequence-dependent conformation, in a similar manner to the indirect readout mechanism in protein-DNA recognition. We used a knowledge-based technique that takes advantage of known DNA structures to evaluate the conformational energies. We built a dataset of non-redundant free B-DNA crystal structures to calculate the distributions of adjacent base-step and base-pair conformations, and estimated the effective harmonic potentials of mean force (PMF). These PMFs were used to calculate the conformational energy of drug-DNA complexes, and the Z-sco

SUBMITTER: Arauzo-Bravo MJ 

PROVIDER: S-EPMC2241865 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature