VRML IN CANCER-RESEARCH - LOCAL CHANGES IN BINDING-PROPERTIES OF WILD-TYPE AND MUTATED P53 TUMOR-SUPPRESSOR PROTEIN

The inactivation of the p53 tumor suppressor function by single missen se point mutations is found in almost half of human tumors. Most p53 m utation hotspots are at the DNA binding interface, shown in the three- dimensional (3D) structure of a p53-DNA complex crystallized by Pavlet ich and coworkers [1]. We have investigated the influence of mutations on the predicted specific DNA binding capacities of p53 by using mole cular modeling to compare biochemical properties of wild type and muta ted p53 complexed to DNA. Changes in local properties e.g. electrostat ic potential or hydrophilic/lipophilic properties, combined with the s teric interferences, lend to a loss of specific binding and presumably disables the tumor suppressor function. The 3D-structures combined wi th molecular biochemical properties of the wild type and the mutated p 53-DNA complex can be transferred by the use of the Virtual Reality Mo deling Language (VRML). Special tools e.g. 'space buttons' allow users the interactive exploration of structures, properties, and additional information via internet.