Local Structures in Proteins from Microsecond Molecular Dynamics Simulations: 2. The Role of Symmetry in GTPase...

The Rho GTPase binding domain of Plexin-B1 (RBD) prevails in solution as dimer. Under appropriate circumstances, it binds the small GTPase Rac1 to yield the complex RBD-Rac1. Here, we study RBD dimerization and complex formation from a symmetry-based perspective using data derived from 1 μs long MD simulations. The quantities investigated are the local potentials, u(MD), prevailing at the N-H sites of the protein. These potentials are statistical in character providing an empirical description of the local structure. To establish more methodical description, a method for approximating them by explicit functions, u(simulated), was developed in the preceding article in this journal issue. These functions are combinations of analytical Wigner functions, D, belonging to the D_2h point group. The D_2h subgroups A_g and B_2u are found to dominate u(simulated); the B_1u subgroup contributes in some cases. The A_g (B_2u) functions have axial or rhombic symmetry. For the first time, local potentials in proteins can be quantitatively characterized in terms of their strength (rhombicity) evaluated by axial A_g (rhombic A_g and B_2u) contributions. Until now, the chain-segment [β₃-L3-β₄] and to some extent the α₂-helix have been associated with GTPase binding. Here, we find that this process causes an increase (decrease) in the potential strength of β₃ and β₄ (the preceding L2 loop and the remote chain-segment [(α₂-helix)-(α₂/β₅-turn)-(β₅-strand)]), suggesting effects of counterbalancing and allostery. There is evidence for the L2 loop being associated with RBD-GTPase binding. Until now only the L4 loop has been associated with RBD dimerization. The latter process is found to cause an increase (decrease) in the potential strength and rhombicity of the L4 loop (the adjacent chain-segment [(α₂-helix)-(α₂/β₅-turn)-(β₅-strand)]), suggesting counterbalancing activity. On average, the RBD dimer features stronger local potentials than RBD-Rac1. The novel information inherent in these findings is mesoscopic in character. Prospects of interest include exploring relation to atomistic force-field parameters.