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<p class="MsoNormal">Dear colleagues,</p>
<p class="MsoNormal">I have a problem with PMF calculations with umbrella sampling. A small part of a big molecule migrates from conformation A to conformation B. Although g_wham computes free energy as positive value of ~70kJ/mol for A->B transformation, an average potential energy of the fragment decreases along the trajectory. So in window that corresponds to state A it is -2292kJ/mol and in window corresponding to state B it is -2379 kJ/mol (and the loss looks roughly linear between A and B). The question is follows: how a sampling along a trajectory of decreasing potential energy can yield positive pmf and vice versa? Are there any ideas of what goes wrong in my simulations?</p>
<p class="MsoNormal">P.S. It was a protein molecule simulated with GROMOS96 FF in spc water box and umbrella sampling was of 12 ns per window.</p><br>
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lex<br>
Post Doctoral Fellow<br>
Genome Sciences Centre<br>
Vancouver, BC<br>
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