Modeling, chemical restraints

The minor perturbation of the DNA structure caused by cis-platin may well not be detected in a cell which has a deficiency in the repair mechanism, whereas a normal cell might have a more selective repair mechanism. Whether this is the mechanism of action of the platinum anticancer drugs still has to be established, but it is the first model which satisfactorily accounts for all the known chemical and structural restraints. In addition, it suggests further modeling experiments with the more effective second generation drugs. 

At first glance, the averaged model would appear to serve most researchers who are looking for a molecular model to help them explain the function of the molecule and rationalize other chemical, spectroscopic, thermodynamic, and kinetic data. On the other hand, you might think that the ensemble and distance-restraint files are of most use to those working to improve structure determination techniques. There are good reasons however, for all researchers to look carefully at the ensemble, as discussed in the next section. 

Model compounds designed to mimic the steric restraint of the proximal histidine in the T structure have lower oxygen affinities than do similar model compounds lacking such restraint, and the degree by which the oxygen affinity is lowered is of the same magnitude as in the T compared with the R structure, which shows that the concept of steric restraint is viable chemically. 

Important restraints on the evolution of superior chemical models are the inadequacies in the 1) capability to characterize the organic ligands of natural waters 2) knowledge of redox status of waters, which does not permit realistic computation of redox-controlled speciation 3) available thermodynamic data ... 

---