DNA-psoralens molecular recognition using molecular dynamics

Furocoumarins are an important class of compounds for photochemotherapy use d in the treatment of numerous diseases characterised by hyperproliferative conditions. Their photosensitising activity has been related to the abilit y to form covalent linkage with the pyrimidine bases of DNA upon UV-A irrad iation. Using the published experimental data of the 3D-structure of the fu ran-side monoadduct between the 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen and the DNA oligonucleotide d(GCG-TACGC)(2) as starting point, a computati onal procedure to study the dark intercalation complexes by molecular dynam ics was built and then preliminary validated on another psoralen. This dock ing procedure provides a tool to better understand the mechanism of the DNA -intercalation of these linear furocoumarins and it can be useful in the de sign of new photochemotherapeutic agents with an improved therapeutic profi le. (C) 1999 Elsevier Science S.A. All rights reserved.