Molecular dynamics simulation of membrane peptides with an implicit membrane model

Molecular dynamics simulation is a powerful technique to study structure and function of biological systems. Over the time, by developing more sophisticated models and faster computers, interest in simulating larger and more complicated systems has grown. With the current supercomputers, molecular dynamics simulation of huge systems, which we could only dream of several years ago, has become possible but yet computationally expensive. Implicit treatment of the solvent (and membrane) is one of the widely used methods to reduce the computational costs, which also can be used in combination with other enhanced sampling methods. However, there is still some room for improving both the accuracy and the speed of such methods.;Molecular dynamics simulations of Phospholamban (PLB) have been carried out with the Heterogeneous Dielectric Generalized Born method (HDG) with an implicit representation of the solvent and membrane. The conformational sampling of PLB in the phosphorylated and unphosphorylated states suggests that PLB has a steric effect on the E2-E1 conformational transition of Sarcoplasmic Reticulum Ca2+-ATPase (SERCA). This steric effect disrupts the Ca2+ ion uptake cycle and inhibits SERCA. Phosphorylation of PLB at Ser16 induces some structural changes in the PLB that diminishes the steric effect and allows SERCA to visit the E1 state and transports Ca +2 ion.;A Hamiltonian replica exchange has been also introduced to enhance sampling in the implicit solvent simulations. In this technique, the solvent's dielectric constant exchanges between the replicas. It is proposed that visiting replicas with the lower dielectric constants alters the energy surface and improves the sampling speed.