Multistep modeling of protein structure: application to bungarotoxin

Modelling of bungarotoxin in atomic details is presented in this article. The model-building procedure utilizes the low-resolution crystal coordinates of the c-alpha atoms of bungarotoxin, sequence homology within the neurotoxin family, as well as high-resolution x-ray diffraction data of cobratoxin and erabutoxin. Our model-building procedure involves: (a) principles of comparative modelling, (b) embedding procedures of distance geometry, and (c) use of molecular mechanics for optimizing packing. The model is not only consistent with the c-alpha coordinates of crystal structure, but also agrees with solution conformational features of the triple-stranded beta sheet as observed by NOE measurements.