Time-averaged nuclear Overhauser effect distance restraints applied to tendamistat.
A penalty function is introduced into molecular dynamics simulations that improves on current methods for enforcing nuclear magnetic resonance-based distance restraints. Rather than treating nuclear Overhauser effects as static distance bounds, they are considered as quantities that must be satisfied on average over the course of a simulation trajectory. The efficacy of the method is demonstrated on the previously determined structure of tendamistat. The molecular dynamics simulations show that the time-averaged constraints increase the mobility allowed to molecules, produce better agreement with distance bounds, improve searching properties and give a better estimate of the conformational space occupied by the molecule in solution.
Torda
A E
AE
Laboratory of Physical Chemistry, University of Groningen, The Netherlands.
Scheek
R M
RM
van Gunsteren
W F
WF
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D011487:Protein Conformation; D013997:Time Factors
D010455:Peptides; C030526:tendamistate