Browsing by Author "Gunsteren, Wilfred F. van"

Now showing 1 - 2 of 2

Open Access
On the use of 3J-coupling NMR data to derive structural information on proteins
(2021) Smith, Lorna J.; Gunsteren, Wilfred F. van; Stankiewicz, Bartosz; Hansen, Niels
Values of 3J-couplings as obtained from NMR experiments on proteins cannot easily be used to determine protein structure due to the difficulty of accounting for the high sensitivity of intermediate 3J-coupling values (4-8 Hz) to the averaging period that must cover the conformational variability of the torsional angle related to the 3J-coupling, and due to the difficulty of handling the multiple-valued character of the inverse Karplus relation between torsional angle and 3J-coupling. Both problems can be solved by using 3J-coupling time-averaging local-elevation restraining MD simulation. Application to the protein hen egg white lysozyme using 213 backbone and side-chain 3J-coupling restraints shows that a conformational ensemble compatible with the experimental data can be obtained using this technique, and that accounting for averaging and the ability of the algorithm to escape from local minima for the torsional angle induced by the Karplus relation, are essential for a comprehensive use of 3J-coupling data in protein structure determination.
Open Access
On the use of side‐chain NMR relaxation data to derive structural and dynamical information on proteins : a case study using hen lysozyme
(2020) Smith, Lorna J.; Gunsteren, Wilfred F. van; Hansen, Niels
Values of S2CH and S2NH order parameters derived from NMR relaxation measurements on proteins cannot be used straightforwardly to determine protein structure because they cannot be related to a single protein structure, but are defined in terms of an average over a conformational ensemble. Molecular dynamics simulation can generate a conformational ensemble and thus can be used to restrain S2CH and S2NH order parameters towards experimentally derived target values S2CH(exp) and S2NH(exp). Application of S2CH and S2NH order‐parameter restraining MD simulation to bond vectors in 63 side chains of the protein hen egg white lysozyme using 51 S2CH(exp) target values and 28 S2NH(exp) target values shows that a conformational ensemble compatible with the experimentally derived data can be obtained by using this technique. It is observed that S2CH order‐parameter restraining of C-H bonds in methyl groups is less reliable than S2NH order‐parameter restraining because of the possibly less valid assumptions and approximations used to derive experimental S2CH(exp) values from NMR relaxation measurements and the necessity to adopt the assumption of uniform rotational motion of methyl C-H bonds around their symmetry axis and of the independence of these motions from each other. The restrained simulations demonstrate that side chains on the protein surface are highly dynamic. Any hydrogen bonds they form and that appear in any of four different crystal structures, are fluctuating with short lifetimes in solution.