Molecular properties of amphotericin B membrane channel: A molecular dynamics simulation

Amphotericin B is a powerful but toxic antifungal antibiotic that is used to treat systemic infections. It forms ionic membrane channels in fungal cells. These antibiotic/sterol channels are responsible for the leakage of ions, which causes cell destruction. The detailed molecular properties and structure of amphotericin B channels are still unknown. In the current study, two molecular dynamic simulations were performed of a particular model of amphotericin B/cholesterol channel. The water and phospholipid environment were included in our simulations, and the results obtained were compared with available experimental data. It was found that it is mainly the hydrogen bonding interactions that keep the channel stable in its open form. Our study also revealed the important role of the intermolecular interactions among the hydroxyl, amino, and carboxyl groups of the channel-forming molecules; in particular, some hydroxyl groups stand out as new ''hot spots'' that are potentially useful for chemotherapeutic investigations. Our results also help to clarify why certain antibiotic derivatives, with a blocked amino group, are less active. We present a hypothesis for the role of membrane lipids and cholesterol in the channel.