Thermodynamics and stability of a β-sheet complex: Molecular dynamics simulations on simplified off-lattice protein models

摘要

We have performed discontinuous molecular dynamics simulations of the thermodynamics and stability of a tetrameric β-sheet complex that contains four identical four-stranded antiparallel β-sheet peptides. The potential used in the simulation is a hybrid Go-type potential characterized by the bias gap parameter g, an artificial measure of the preference of a model protein for its native state, and the intermolecular contact parameter η, which measures the ratio of intermolecular to intramolecular native attractions. Despite the simplicity of the model, a complex set of thermodynamic transitions for the β-sheet complex is revealed that shows there are three distinct oligomer (partially ordered, ordered, and highly ordered β-sheet complex) states and four noninteracting monomers phases. The thermodynamic properties of the three oligomer states strongly depend on both the size of the intermolecular contact parameter η and the temperature. The partially ordered β-sheet complex is made up of four ordered globules and is observed at intermediate to large η at high temperatures. The ordered β-sheet complex contains four native β-sheets and is located at small to intermediate η at low temperatures in the phase diagram. The highly ordered β-sheet complex has fully-stiff β-sheet strands, the same as the global energy minimum structure, and is observed for all η at low temperatures.