The study of possible A and B conformations of alternating DNA using a new program for conformational analysis of...

A new program, CONAN has been designed for CONformational ANalysis of oligonucleotide duplexes with natural and modified bases. It allows to model both regular DNA fragments with different types of symmetry and irregular ones including bends, junctions, mismatched pairs and base lesions. Computations and minimization of the energy are performed in a space of internal structural variables chosen to build start structure easier and conveniently analyze the results obtained. These internal structural variables determine mutual base-base and base-sugar arrangement and sugar puckering. The analytical closure procedure is applied both to sugar rings and to backbone fragments between adjacent sugars. For more effective energy minimization, analytical gradient is calculated. The CONAN was applied to the search for low-energy conformations of poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC) duplexes. Extended regions of low-energy A and B conformations are revealed and characterized. These regions contain structures with different relative values of helical twist, tau, for pur-pyr and pyr-pur steps, namely, conformations with tau (pur-pyr) > tau (pyr-pur) and with tau (pur-pyr) < tau (pyr-pur). Two types of sugar puckering were found for B-form low-energy conformations, the first type with all C2'-endo sugar residues and the second one - with C2'-endo purines and O1'-endo pyrimidines. The calculated conformations are compared with X-ray diffraction data for crystals and fibers and NMR data for solution.