Molecular modelling of amphotericin B–ergosterol primary complex in water

The properties of amphotericin B–ergosterol primary complex have been studied with the use of the molecular dynamics simulation. Possible geometries of the complex were tested first in order to find the structures with the most favourable values of the intermolecular interactions energy. The molecules studied possessed a tendency to fit each other's shapes, which favours intermolecular van der Waals interactions. The main simulations were performed for the best structures found. Presence of hydrogen bonds between the sterol hydroxyl group and polar fragments of mycosamine (most frequently 2′OH) was coupled with a relatively high level of the intermolecular energy values. The structures obtained are hardly comparable to the hypothetical and ‘computational’ models of the antibiotic–sterol complex. The geometries found are not suitable to assemble the presupposed structure of the water channel, however, the existence of the complex in the shape anticipated is not in contradiction to the results of biophysical experiments on the complexation in water and in hydroalcoholic media.