Modeling of the 3RS tau protein with self-consistent field method and Monte Carlo simulation

Abstract

Using a model with amino acid resolution of the 196 aa N-terminus of the 3RS tau protein, we performed both a Monte Carlo study and a complementary self-consistent field (SCF) analysis to obtain detailed information on conformational properties of these moieties near a charged plane (mimicking the microtubule surface). The SCF model implements a second level of coarse graining wherein amino acids are grouped according to charge and solvency properties. In the low ionic strength regime, both approaches give very similar predictions for the concentration dependence, namely that the tau fragment has a compact fence-like structure near the surface and an extended tail pointing away from the surface. The correspondence between the two approaches is remarkable considering the vast difference in computational effort. The MC method samples self-avoiding conformations in a continuum space and predicts both lateral as well as normal distributions, whereas the SCF analysis uses a freely-jointed chain model on a lattice in combination with mean-field approximations and focuses merely on the concentration profile normal to the interface. Motivated by the good correspondence, we use the SCF approach to explore various consequences of the choices made in the MC analysis.