MOLECULAR-DYNAMICS OF AMPHOTERICIN-B .2. DIMER IN WATER

Molecular dynamics simulations were performed for a dimer of the antif ungal antibiotic, amphotericin B, in water. In the first step of the w ork three appropriately selected versions of the dimer structure were taken into consideration. In each version antibiotic molecules were pl aced antiparallel with polar and ionizable groups outside the hydropho bic core formed by polyene chromophores. During short dynamic simulati ons versions of the dimer structure were compared in respect of the en ergy of dimerization. The highest energy was observed for the structur e in which polyene chromophores superimposed each other as much as pos sible and this version was subjected to the main simulation. The analy sis of 66 snapshot geometries stored during 33 ps dynamic trajectory a llowed us to draw three main conclusions: (i) the relative orientation of the amino-sugar moiety and chromophore as well as conformation of the antibiotic macrolide ring were different in both molecules and cou ld exhibit dynamic changes, (ii) the dimer structure exhibited intrins ic asymmetry which could be responsible for characteristic circular di chroism spectra of the aggregated form of the antibiotic, (iii) relati vely high stability of the dimer structure resulted not only from hydr ophobic interactions between chromophores but also from hydrogen bonds networks that were observed around polar terminals of antibiotic mole cules. Implications of these features of the dimer structure for its s usceptibility on the ionic state of carboxyl and/or amino groups are a lso discussed.