McCarthy S L, Hinde R J, Miller K J, Anderson J S, Basch H, Krauss M
Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12180.
Biopolymers. 1990 Mar-Apr;29(4-5):823-36. doi: 10.1002/bip.360290416.
The binding of cis-Pt(II) diammine (cis-DP) to double-stranded DNA was studied with several kinked conformations that can accommodate the formation of a square planar complex. Molecular mechanics (MM) calculations were performed to optimize the molecular fit. These results were combined with quantum mechanical (QM) calculations to ascertain the relative energetics of ligand binding through water vs direct binding of the phosphate to the ammine and platinum, and to guide the selection of DNA conformations to model complex formation. Based on QM and MM calculations, models are proposed that may be characterized by several general features. A structure involving hydrogen bonding between each ammine and distinct adjacent phosphate groups, referred to as closed conformation (CC), has already been reported. This is also found in the crystal structure of small dimers. We report alternative conformations that may be important in platination of duplex DNA. They are characterized by an intermediate conformation (IC), involving hydrogen bonding between one ammine and phosphate group, and an open conformation (OC), without ammine phosphate hydrogen bonding. The IC and OC can be stabilized by water bridges in the space between the ammine and the phosphate groups. Sugar puckers alternate from the type C(2')-endo or C(1')-exo (S), to the type C(3')-endo or C(2')-exo (N), with intermediate types near O(1')-endo (O). In general, the sugar puckers alternate from S to N to S through the platinated region (3'-TpGpGp-5'), with the complexed strand exhibiting, (3')-S*-N*-S-(5') alternation, while the complementary strand shows either (3')-S*-N*-S-(5') or (3')-S*-N*-O-(5') alternation. In both the OC and IC, a hydrogen bond is found between the ammine and O4(T) on thymine (T) at the (3') end, adjacent to the complex site. There is a continuous range of backbone conformations through the platinated region which relate the OC to the IC. The models presented suggest that the dynamics of the binding of the cis-Pt(II)-diammines to adjacent N7(G) in double-stranded DNA may encompass several conformational possibilities, and that water bridges may play a roll in supporting open and intermediate conformations. Proton-proton distances are reported to assist in the experimental determination of conformations.
研究了顺铂（II）二胺（cis-DP）与几种扭结构象的双链DNA的结合，这些构象能够容纳平面四边形配合物的形成。进行了分子力学（MM）计算以优化分子拟合。这些结果与量子力学（QM）计算相结合，以确定通过水的配体结合与磷酸直接与胺和铂结合的相对能量，并指导选择用于模拟配合物形成的DNA构象。基于QM和MM计算，提出了可能具有几个一般特征的模型。已经报道了一种涉及每个胺与不同相邻磷酸基团之间氢键的结构，称为封闭构象（CC）。这也在小的二聚体的晶体结构中发现。我们报道了在双链DNA的铂化过程中可能重要的替代构象。它们的特征在于中间构象（IC），涉及一个胺与磷酸基团之间的氢键，以及开放构象（OC），没有胺-磷酸氢键。IC和OC可以通过胺和磷酸基团之间空间中的水桥来稳定。糖的构象从C(2')-内向或C(1')-外向（S）型交替为C(3')-内向或C(2')-外向（N）型，在O(1')-内向（O）附近有中间类型。一般来说，糖的构象通过铂化区域（3'-TpGpGp-5'）从S交替为N再到S，络合链表现出（3'）-S*-N*-S-（5'）交替，而互补链则表现出（3'）-S*-N*-S-（5'）或（3'）-S*-N*-O-（5'）交替。在OC和IC中，在（3'）端与络合位点相邻的胸腺嘧啶（T）上的胺与O4（T）之间发现了氢键。通过铂化区域存在连续范围的主链构象，将OC与IC联系起来。所提出的模型表明，顺铂（II）-二胺与双链DNA中相邻N7（G）的结合动力学可能包含几种构象可能性，并且水桥可能在支持开放和中间构象中起作用。报道了质子-质子距离有助于构象的实验测定。
