Abstract: Atomic details of the peptide-membrane interactions are not accessible with most experimental means; computational methods can provide this information complementing the experimental macroscopic views. In this talk, I will present how we utilized multi-scale molecular dynamics approaches to simulate the interfacial folding and membrane insertion of Ab(25-35) peptide and Indolicidin antimicrobial peptide in a spontaneous fashion. For the Ab(25-35) peptide study, I will demonstrate how we correlated the configurations of Ab(25-35) peptide and its mutants within membrane with their relative neurotoxicities from the simulation results (Proteins 2010). For the study of Indolicidin antimicrobial peptide, I will show how we differentiate its antimicrobial and hemolytic mechanisms from microscopic point of view (J. Mol. Biol. 2009). Using the mechanisms derived from simulations, we have successfully designed a de novo peptide with higher antimicrobial activity and lower hemolytic activity simultaneously (in vitro).