Starting structure dependence of NMR order parameters derived from MD simulations: implications for judging force-field quality - PubMed (original) (raw)

Starting structure dependence of NMR order parameters derived from MD simulations: implications for judging force-field quality

Alrun N Koller et al. Biophys J. 2008 Jul.

Abstract

Comparing experimental generalized N-H S(2) order parameters to those calculated from molecular dynamics trajectories is increasingly used to judge force-field quality and completeness of sampling. Herein we demonstrate for the well-investigated system hen egg white lysozyme that different experimental starting structures can lead to significant differences in molecular-dynamics-derived S(2) parameters that can be even larger than S(2) parameter deviations due to different force fields. Caution should thus be taken in general when simulated S(2) parameters are compared to experimental data with the aim of judging force-field quality. We show that adequately sampling flexible regions ( approximately 100 ns) and only calculating S(2) parameters averaged over short time windows proved necessary to obtain consistent results irrespective of the starting structure.

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Figures

FIGURE 1

FIGURE 1

(a) Residues 65–75 (loop 2) of the investigated HEWL structures (1HEL (orange, cluster 1); 1E8L model 1 (cyan, cluster 1); 1IEE (green, cluster 2); and 6LYT (magenta, cluster 4)). The N atoms of Gly71 and Asn74 are colored in yellow. Additionally, it is indicated if the N-H bond points to the protein (p) or to the solvent (s). (b) Experimental _S_2 values (18) (black) are compared to calculated values (green) from the 30 ns simulation of 1IEE with ff99SB. Secondary structure elements are indicated by boxes (white, helix; gray, _β_-sheet). (c) Comparison of experimental (18) (black) and calculated _S_2 values (colored as in a) of loop 2 using ff99 and ff99SB. The _S_2 values were either calculated over the whole 30 ns trajectory (left panels) or averaged over time windows of 1 ns length (right panels). The red line depicts 1 ns time window-averaged _S_2 values of 1HEL over 100 ns.

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