Detailed atomistic molecular dynamics simulations of alpha-conotoxin AuIB in water.

We present results about the shape, size, structure, conformational stability, and hydrodynamics of alpha-conotoxin AuIB (a disulfide-rich peptide from the venom of Conus aulicus, recognized as a nicotinic acetylcholine antagonist with great pharmaceutical potential) from very long (0.5 mus) massively parallel molecular dynamics (MD) simulations in full atomistic detail. We extract coarse-grained descriptors of protein shape (ellipsoid), and of translational and rotational mobilities, i.e., the basic components at the lowest hierarchical level in a multiscale modeling strategy. Structural analysis reveals the folded conformation and asymmetric shape to be strongly favored for conotoxin. In accordance with experimental findings, conformational stability is observed and found to be linked to the presence of the alpha-helix along the 15 residues and to the existence of the two disulfide bonds. We find rotational (D(r)) and translational (D(t)) diffusivities to be suitable descriptors of coarse-grained dynamics, i.e., of the hydrodynamic behavior, and obtain D(r) = 3.62 (+/-0.17) x 10(8) s(- 1) and D(t) = 1.08 (+/-0.4) x 10(- 10) m(2) s(- 1). We further compare the MD-computed coarse-grained descriptors with first principles theoretical predictions based on the extended Hess-Doi Fokker-Planck approach which relates particle shape and dimensions to diffusion coefficients. An excellent agreement between simulation data and analytical predictions is observed for both dynamical descriptors. This comparison strongly suggests that diffusivities of rigid biomolecules much larger than the alpha-conotoxin AuIB studied here can be obtained from the coarse-grained shape descriptor (ellipsoid) derived from relatively short MD simulations.