What is the purpose of your umbrella sampling (US) molecular dynamics (MD) simulation?
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1. Define the "reaction" coordinate of the process you want to simulate.
2. Run restrained MD simulation at each step (window) along the reaction coordinate.
3. Calculate the potential of mean force (PMF) of the "reaction" from overlapping windows: Weighted histogram analysis method (WHAM).
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And the caveat: The ideal choice of the "reaction" coordinate requires knowing the solution beforehand. Several attempts using different values for the restraints and different number of windows might be needed to get the feeling about what the system needs to behave properly. MD/US is a "black magic" rather than a "black box" approach.
A "cheaper" (but not necessarily less accurate) alternative based on the linear response theory: Linear Interaction Energy (LIE) method developed by Aqvist.
Hansson et al. (1998) J Comput Aided Mol Des 12: 27-35.
https://www.ncbi.nlm.nih.gov/pubmed/9570087
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