On using oscillating time-dependent restraints in MD simulation.
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 (3) J-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 (3) J-coupling constants measured in NMR experiments to the corresponding torsional-angle values cause severe problems when trying to restrain a (3) J-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.
Keller
Bettina
B
Laboratorium für Physikalische Chemie, ETH Zürich, Zürich, CH-8093, Switzerland.
Christen
Markus
M
Oostenbrink
Chris
C
van Gunsteren
Wilfred F
WF
D000465:Algorithms; D002073:Butanes / Q000737:chemistry; D003198:Computer Simulation; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010456:Peptides, Cyclic / Q000737:chemistry
D002073:Butanes; D010456:Peptides, Cyclic; C100265:antamanide; C046888:butane