FORCE-FIELD FOR PLATINUM BINDING TO ADENINE AND GUANINE TAKING INTO ACCOUNT FLEXIBILITY OF NUCLEIC-ACIDS BASES

Many metal-based antitumor drugs such as cis-diamminedichloroplatinum( II) (cisplatin) bind to purine nucleic acid (NA) bases via N7. On the basis of ab initio quantum mechanics calculations using [Pt(NH3)(3) pu rine](2+) (where purine = adenine or guanine) as a model system, we sh ow that the common assumption of planarity of NA bases leads to an ove restimation of the platinum out-of -plane bending molecular mechanics constant in certain cases by more than 50%. New values of force-field parameters are given, and some of the implications on molecular mechan ics computations of platinum nucleic acid adducts are discussed.