| Heterogeneous dielectric generalized Born (HDGB) model has been applied to study the conformational sampling of the influenza fusion peptide (IFP) in the context of membrane bilayers. The dominant structure of the IFP shows a tight break in the middle region and interfacial insertion in the membrane bilayer. Different protonation states of titratable residues in the IFP sequence were also simulated and the results show that the pH has little effect on the configuration of the peptide in the membrane.;The conformational sampling of the Ebola fusion peptide (EFP) in the membrane environment and water was also studied using the implicit membrane/solvent model. The EFP shows to be strongly sensitive to its neighboring residues and it adopts different conformation in their presence. It also tends to have more extended structure in water compared to the membrane environment. However, its overall structure in the membrane bilayer was observed to be helical in the middle region and extended in the N and C terminal parts.;The overall comparison between the results obtained from simulations and experimental observations for these peptides proves that the HDGB model is capable of capturing the peptide- membrane interactions. However, in all current implicit membrane models, including HDGB, the static structure of the membrane bilayer and lack of fluctuations in the local thickness and curvature of the membrane does not allow the bilayer to respond to the presence of a charged particle or any hydrophobic mismatch in general. This would in particular, lead to overestimation of insertion energy barriers of charged particles. In the improved implicit membrane model called dynamic heterogeneous dielectric generalized Born (DHDGB), these problems are being addressed by introducing extra degrees of freedom to represent the membrane fluctuations. The effect of membrane dynamics on different test systems has also been studied and the results are being presented and discussed. |
