(722h) Pore Formation By Aggregates of Melittin in 1,2-Dioleoyl-Sn-Glycero-3-Phosphocholine (DOPC) and 1,2-Di-(9Z-octadecenoyl)-Sn-Glycero-3-Phospho-(1'-rac-glycerol) (DOPG) Mixed Lipid Bilayer | AIChE

(722h) Pore Formation By Aggregates of Melittin in 1,2-Dioleoyl-Sn-Glycero-3-Phosphocholine (DOPC) and 1,2-Di-(9Z-octadecenoyl)-Sn-Glycero-3-Phospho-(1'-rac-glycerol) (DOPG) Mixed Lipid Bilayer

Authors 

Narsimhan, G. - Presenter, Purdue University
Lyu, Y., Purdue University
Xiang, N., Purdue University
Zhu, X., Purdue Univerrsity
Antimicrobial peptides (AMP) inactivate microorganisms by forming pores in cell membrane. Since their mechanism of action differs from that of antibiotics, they could be very useful for combating drug resistant microbes, for treatment of microbial infections and also for prevention. Elucidation of mechanism of pore formation will help in the design of synthetic AMP for specific microorganism. This study characterizes (i) pore formation and (ii) the potential of mean force for peptide insertion, through molecular dynamics (MD) simulation for melittin, a naturally occurring AMP, into a DOPC/DOPG mixed bilayer. Critical peptide/lipid ratio was observed for penetration of melittin from the surface as well as for water channel formation for transmembrane peptides. The phospholipid density profile across the bilayer indicated a toroidal pore structure. The energy barrier for insertion of a melittin molecule decreased for insertion into a pore with larger number of transmembrane peptides eventually approaching zero. Water channel formation occurred only for insertion into pores consisting of four or more transmembrane peptides with the radius of water channel being larger for larger number of transmembrane peptides. A mathematical model for the evaluation of energy barrier for formation of pore consisting of peptide aggregates of different size interspersed with phospholipid head was proposed which considers detailed pore structure as well as intermolecular interactions. Estimated free energy barrier for insertion of melittin into an ideal paraboloid pore were consistent with MD simulation results. The model was employed to elucidate the rates of formation and dissociation of pores by AMP and nucleation of pores in lipid bilayers.