PROBING THE UNDERLYING BASIS FOR THE BINDING-SPECIFICITY OF CALICHEAMICIN GAMMA(1)(I) - A MOLECULAR-DYNAMICS STUDY

Six different models of the DNA-calicheamicin complex were constructed to investigate the mode of binding of the rhamnose, thiobenzoate and thiosugar residues of the carbohydrate-thiabenzoate tail of calicheami cin with DNA. The stability of each model was tested in a 500 psec sol vated molecular dynamics simulation. Five of the six models predicted the correct DNA hydrogen abstraction pattern. However, only one model was found to be consistent with air of the available experimental data and provided a clear rationale for the observed 5'-TCCT/3'AGGA sequen ce specificity.