A MOLECULAR MECHANICAL STUDY OF NETROPSIN-DNA INTERACTIONS

We present molecular mechanical calculations on the complexes of netropsin with dA6.cntdot.dT6, d(TATATA)2, d(CGCGCG)2, and d(CGCGAATTCGCG)2. The complexes were model built using computer graphics and then completely energy refined. Our calculations are consistent with the observed AT preference for netropsin and suggest that mixed sugar pucker geometries should be more stable than uniform in netropsin complexes with poly[d(A-T)].cntdot.poly[d(A-T)] and poly(dA).cntdot.poly(dt). The netropsin-d(TATATA) and netropsin.cntdot.dA6.cntdot.dT6 complexes are significantly different in structure, leading to a possible reason why the observed thermodynamics of netropsin-association with poly[d(A-T)].cntdot.poly[d(A-T)] and with poly(dA).cntdot.poly(dT) are so different. We also model built and energy refined a structure of netropsin-d(CGCGAATTCGCG)2 using as a guide the nmr data of Patel [(1982) Proc. Natl. Acad. Sci. USA, 79, 6424-6428], and found a three-dimensional structure qualitatively consistent with the NOE enhancements observed by him. After our calculations were completed, we learned of an X-ray structure of a netropsin:d(CGCGAATTCGCG)2 complex, and we compared the structure found in our calculation with the X-ray structure.