Abstract
The use of time-dependent restraints in molecular simulation in order to generate a conformational ensemble for molecules that is in accordance with measured ensemble averages for particular observable quantities is investigated. Using a model system consisting of liquid butane and the cyclic peptide antamanide the reproduction of particular average 3J-coupling constant values in a molecular dynamics simulation is analysed. It is shown that the multiple-valuedness and the sizeable gradients of the Karplus curve relating 3J-coupling constants measured in NMR experiments to the corresponding torsional-angle values cause severe problems when trying to restrain a 3J-coupling constant to a value close to the extrema of the Karplus curve. The introduction of a factor oscillating with time into the restraining penalty function alleviates this problem and enhances the restrained conformational sampling.
Original language | English |
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Pages (from-to) | 1-14 |
Number of pages | 14 |
Journal | Journal of Biomolecular NMR |
Volume | 37 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2007 |
Funding
Financial support by the National Centre of Competence in Research (NCCR) Structural Biology and by grant 200021-109227 of the Swiss National Science Foundation (SNSF) is gratefully acknowledged.
Keywords
- J-coupling constants
- Molecular modeling
- NMR data
- Restrained MD
- Structure refinement