Molecular dynamics (MD) and Monte Carlo (MC) methods are used to determine the spin-pair correlation function, G * (t), for the diffusion of bulk water in three-dimensions (3D) and pore water in two-dimensions (2D) and quasi-two-dimensions (Q2D). The correlation function is required for the determination of the nuclear magnetic resonance (NMR) spin-lattice and spin-spin relaxation times T 1 and T 2 . It is shown that the analytic form of the powder-average correlation function, introduced by Sholl [C. A. Sholl, J. Phys. C: Solid State Phys. 7, 3378 (1974)] for the diffusion of spins on a 3D lattice, is of general validity. An analytic expression for G * (t) for a uniform spin fluid is derived in 2D. An analytic expression for the long-time behaviour of G * (t) is derived for spins diffusing on 3D, 2D and Q2D lattices. An analytic correction term, which accounts for spin-pairs outside the scope of the numerical simulations, is derived for 3D and 2D and shown to improve the accuracy of the simulations. The contributions to T 1 due to translational and rotational motion obtained from the MD simulation of bulk water at 300 K are 7.4 s and 10±1 s respectively, at 150MHz leading to an overall time of 4.3 ± 0.4 s compared the experimental value of 3.8 s. In Q2D systems, in which water is confined by alpha-quartz surfaces to thicknesses of 1-5 nm, T 1 for both translational and rotational relaxation is reduced due to the orientation and adsorption of spins at the surfaces. A novel method of parameterising the MC lattice-diffusion simulations in 3D, 2D and Q2D systems is presented. MC results for G * (t) for 3D and 2D systems are found to be consistent with an analytic uniform fluid model for t 40 ps. The value of T 1 for translational diffusion obtained from the MC simulation of bulk water is found to be 4.8 s at 15 MHz. G * (t) obtained from MC simulations of Q2D systems, where water is confined by hard walls, is found to execute a distinct transition from 3D to 2D behaviour. The T 1 is found to be similar to the 3D bulk water result at all pore thicknesses.

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Factor H (FH) is the major regulator of C3b in the alternative pathway of the complement system in immunity. FH comprises 20 short complement regulator (SCR) domains, including eight glycans, and its Y402H polymorphism predisposes those who carry it to age-related macular degeneration. To better understand FH complement binding and self-association, we have studied the solution structures of both the His-402 and Tyr-402 FH allotypes. Analytical ultracentrifugation revealed that up to 12% of both FH allotypes self-associate, and this was confirmed by small-angle X-ray scattering (SAXS), MS, and surface plasmon resonance analyses. SAXS showed that monomeric FH has a radius of gyration (Rg) of 7.2–7.8 nm and a length of 25 nm. Starting from known structures for the SCR domains and glycans, the SAXS data were fitted using Monte Carlo methods to determine atomistic structures of monomeric FH. The analysis of 29,715 physically realistic but randomized FH conformations resulted in 100 similar best-fit FH structures for each allotype. Two distinct molecular structures resulted that showed either an extended N-terminal domain arrangement with a folded-back C terminus or an extended C terminus and a folded-back N terminus. These two structures are the most accurate to date for glycosylated full-length FH. To clarify FH functional roles in host protection, crystal structures for the FH complexes with C3b and C3dg revealed that the extended N-terminal conformation accounted for C3b fluid-phase regulation, the extended C-terminal conformation accounted for C3d binding, and both conformations accounted for bivalent FH binding to glycosaminoglycans on the target cell surface.

Nuclear magnetic resonance (NMR) relaxation experimentation is an effective technique for probing the dynamics of proton spins in porous media but interpretation requires the application of appropriate spin diffusion models. Molecular dynamics (MD) simulations of porous silicate-based systems containing a quasi-two-dimensional water-filled pore are presented. The MD simulations suggest that the residency time of the water on the pore surface is in the range 0.03-12 ns, typically 2-5 orders of magnitude less than values determined from fits to experimental NMR measurements using the established surface-layer (SL) diffusion models of Korb and co-workers [Phys. Rev. E 56, 1934Rev. E 56, , (1997]. Instead, MD identifies four distinct water layers in a tobermorite-based pore containing surface Ca 2+ ions. Three highly-structured water layers exist within 1 nm of the surface and the central region of the pore contains a homogeneous region of bulk-like water. These regions are referred to as layer 1 and 2 (L1, L2), transition layer (TL) and bulk (B), respectively. Guided by the MD simulations, a two-layer (2L) spin-diffusion NMR relaxation model is proposed comprising two two-dimensional layers of slow-and fast-moving water associated with L2 and layers TL+B respectively. The 2L model provides an improved fit to NMR relaxation times obtained from cementitious material compared to the SL model, yields diffusion correlation times in the range 18-75 ns and 28-40 ps in good agreement with MD, and resolves the surface residency time discrepancy. The 2L model, coupled with NMR relaxation experimentation, provides a simple yet powerful method of characterising the dynamical properties of proton-bearing porous silicate-based systems such as porous glasses, cementitious materials and oil-bearing rocks.