MOLECULAR-DYNAMICS SIMULATION OF A DEOXYDINUCLEOSIDE DRUG INTERCALATION COMPLEX - DCPG/PROFLAVIN

A molecular dynamics (MD) study of the dCpG/proflavin crystal hydrate based on the GROMOS force field and simulation protocol is reported. The objectives of the study are (a) to determine the extent to which the theoretical calculations account for the dynamical motion of the complex and the organization of the water network and (b) to investigate the nature of the intermolecular hydrogen bonding network and determine the extent of interconnections on a static and dynamical basis. The results show the GROMOS energy function to have a well-defined energy minimum with a root-mean-square deviation of 0.19 Å for the complex and 0.38 Å for the water. The hydrogen bond network in the energy-minimized water structure is not as fully connected as was indicated by the 3.2-Å crystallographic contacts. MD calculations were performed on a system of two unit cells (eight asymmetric units) for 25 ps at a temperature of 300 K. The dynamical behavior of the complex was reasonable, even to the point of reproducing mixed sugar puckers. The water structure was examined in terms of a hydrogen bond density representation. Here, in a dynamical sense and symmetry averaged over asymmetric units, the water network was found to be fully hydrogen bonded and consistent with 3.2 Å contact representation. The contact representation is thus a good indication of the time-averaged hydrogen bond network. © 1990 American Chemical Society.