Interaction of HIV-1 Gag matrix domain with plasma membrane from coarse-grained molecular dynamics simulations

We performed coarse-grained simulations with explicit solvent to analyse the role of myristoyl in the matrix domain of the HIV-1 protein Gag that interacts with three models of the lipid bilayer. These models were chosen to represent:(a) the inner membrane of the mammalian plasma membrane, (b) the lipid-raft domains, and (c) a generic cholesterol-free bilayer. The inner plasma membrane is the target for the Gag protein when forming the HIV-1 capsid. The other two models permit investigations of the effects of bilayer composition on the interaction between the matrix domain and the lipid bilayer. Our coarse-grained simulations allow sampling over several hundreds of microseconds, in contrast to other atomistic-detail simulations that can only cover a few microseconds. We measured the probability distributions associated with position and orientation of the myristoyl interacting with the plasma membrane models and quantified the orientational order of the myristoyl inserted into the membrane. We determined the Gibbs free energies (potentials of mean force and torque) associated with the observed probability distributions and determined binding energy values of the order of 8 kT, equivalent to similar to 5 kcal mol(-1) at physiological temperature. Our methods can be applied to other acylated proteins interacting with the plasma membrane. [GRAPHICS] .