Multi-scale computer simulations are proposed to give a molecular understanding to the macroscopic view provided by experimental efforts on the application of aqueous diblock copolymer systems to drug delivery and mechanisms of antimicrobial action. Atomistic computer simulations are traditionally used toward this end; however, the high molecular weight of these systems necessitates the use of mesoscopic simulation methodologies. The mechanisms of degradation, poration and drug release will be investigated by the use of dissipative particle dynamics simulations on hydrolysable diblock vesicles. Free-energy techniques will be employed to examine the microdomain formation by hydrolyzed chains, thought to cause a phase transition to the micellar state. Additionally, the use of simulations will help identify the relationship between the hydrophobic core thickness and the drug loading and delivery characteristics of diblock copolymer worm-like and spherical micelles. Finally, the recent finding that the antimicrobial peptide alamethicin lyses thick diblock membranes raises fundamental questions about peptide-membrane interactions; simulations will be conducted to provide insight into the influence of the membrane properties on antimicrobial action. ? ?
