Showing papers by "Wilfred F. van Gunsteren published in 2017"
TL;DR: It is shown that, by combining sets of different, complementary N MR data as restraints in MD simulations, inconsistencies in the data or flaws in the model and procedures used to derive protein structure from NMR data can be detected, which leads to an improved structural interpretation of such data particularly in more mobile loop regions.
Abstract: The derivation of protein structure from values of observable quantities measured in NMR experiments is a rather nontrivial task due to (i) the limited number of data compared to degrees of freedom of a protein, (ii) the uncertainty inherent to the function connecting an observable quantity to molecular structure, (iii) the finite quality of biomolecular models and force fields used in structure refinement, and (iv) the conformational freedom of a protein in aqueous solution, which requires extensive conformational sampling and appropriate conformational averaging when calculating or restraining to sets of NMR data. The protein interleukin-4 (IL-4) has been taken as a test case using NOE distances, S2 order parameters, and 3J-couplings as test data and the former two types of data as restraints. It is shown that, by combining sets of different, complementary NMR data as restraints in MD simulations, inconsistencies in the data or flaws in the model and procedures used to derive protein structure from NMR ...
3 citations
TL;DR: Using S2 order parameter restraining MD simulations, this paradox has been resolved and high S2 values in relatively disordered parts of a protein may be due to fluctuating networks of hydrogen bonds between the backbone and the side chains, which restrict the motion of N-H bond vectors.
Abstract: At low pH, human growth hormone (hGH) adopts a partially folded state, in which the native helices are maintained, but the long loop regions and side-chain packing become disordered. Some of the S2 order parameters for backbone N-H vectors derived from NMR relaxation measurements on hGH at low pH initially seem contradictory. Three isolated residues (15, 20, and 171) in helices A and D exhibit low order parameter values (<0.5) indicating flexibility, whereas residue 143 in the centre of a long flexible loop region has a high order parameter (0.82). Using S2 order parameter restraining MD simulations, this paradox has been resolved. Low S2 values in helices are due to the presence of a mixture of 310 -helical and α-helical hydrogen bonds. High S2 values in relatively disordered parts of a protein may be due to fluctuating networks of hydrogen bonds between the backbone and the side chains, which restrict the motion of N-H bond vectors.
2 citations