Restraint-driven formation of alpha-helical coiled coils in molecular dynamics simulations

The alpha-helical coiled coil motif is among the first characterized and widely found architecture of protein structures. We report here a fast and reliable approach of simulated annealing molecular dynamics (SA/MD) for predicting the three-dimensional structures of various alpha-helical coiled coils of heptad repeat. One key element of our simulation involves a geometric restraint requiring residues occupying the first and fourth positions of the heptad to orient to the angle of their respective statistical average derived from a survey of coiled-coil structures deposited in the Protein Data Bank. Another is the incorporation of subunit rotation and inversion operations for generating symmetrized protein assemblies during the dynamics simulations. The procedure is fully automated and can be applied to different oligomerization states of identical subunits, as well as both parallel and antiparallel arrangements. Despite simplicity, the formation of five coiled-coil prototype systems driven by the restraint-based SA/MD approach shows that the level of prediction accuracy achieved previously by more elaborate procedures can be retained. The present work thus provides validation of a simulation approach that can be employed to utilize a wide variety of knowledge-based geometric restraints for structural prediction of symmetrical or pseudo-symmetrical protein systems.