An NMR Resource for Structural and Dynamic Simulations of Membranes

Abstract

Computational methods are powerful in capturing the results of experimental studies in terms of force fields that both explain and predict biological structures [1]. Validation of molecular simulations requires comparison with experimental data to test and confirm computational predictions. Here we report a comprehensive database of NMR results for membrane phospholipids with interpretations intended to be accessible by non-NMR specialists. Experimental 13C and 2H NMR segmental order parameters and spin-lattice relaxation times are summarized in convenient tabular form for different lipid head group types, length and degree of acyl unsaturation, and the presence of additives such as detergents and cholesterol. Segmental order parameters give direct information about bilayer structural properties, including the area per lipid and volumetric hydrocarbon thickness [2]. In addition, relaxation rates provide complementary information about molecular dynamics [3]. Particular attention is paid to the magnetic field dependence of NMR relaxation rates in terms of various simplified power laws. Model-free reduction of relaxation studies in terms of a power-law formalism shows relaxation rates for saturated phosphatidylcholines follow a single dispersive trend within the MHz regime. We show how analytical models can guide the continued development of atomistic and coarse-grained force fields. Interpretations suggest that lipid diffusion and collective order fluctuations are implicitly governed by viscoelasticity of the liquid-crystalline ensemble. Collective bilayer excitations are emergent over mesoscopic length scales falling between the molecular and bilayer dimensions, and are important for lipid organization and lipid-protein interactions. Future conceptual advances and theoretical reductions will foster understanding of biomembrane structural dynamics through a synergy of NMR measurements and molecular simulations. [1] R.W. Pastor et al. (2002) Acc. Chem. Res.35, 438-446. [2] H.I. Petrache et al. (2000) Biophys. J.79, 3172-3192. [3] M.F. Brown in Biological Membranes (1996) Birkhäuser, Basel, pp. 175-252.