Investigation on salt bridge interactions of mammalian prion proteins by molecular dynamics simulation

Objective: Salt bridge interaction is one of the most important electrostatic interactions to stabilize the secondary and tertiary structures of protein. To obtain more insight into the molecular basis of prion proteins, the salt bridge networks in two animal prion proteins are studied in this work. Methods: Molecular dynamics (MD) and Flow MD (FMD) simulations are employed to investigate the salt bridges interactions of rabbit prion protein (rPrPc), Syrian hamster prion protein (syPrPc) and the variants of the two prion proteins. Results: The dynamic behaviors of salt bridges are characterized, and the relation between salt bridge interactions and local structures are also discussed. The type of salt bridges in the two prion proteins is divided into the helixloop, intra-helix and inter-helix salt bridges. It is found that the helix-loop salt bridges is more important for the stability of prion proteins than the other two kinds of slat bridge. Conclusion: The Asp201-Arg155 (rS1), Asp177-Arg163 (rS3) and Asp178-Arg164 (syS1) are the important salt bridges to stabilize the structures of rPrPc and syPrPc, respectively. The structural stability is partly depended on the number of helix-loop salt bridge.