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free energies calculations (fwd)
Sender: Shawn Huston <shawn@wucmd.wustl.edu>
Subject: WSN: free energies calculations
Dear Rafael,
Do you know you've asked a much asked question? This is what
everyone wants to know. OK, we're all comfortable with the notion that Hphobic
effects lead to a favorable H-H contact energy, but there seems to be some
confusion over whether or not intramolecular HBond formation is
intrinsically favorable or not. (For the moment, I'll limit discussion of
P-P contacts to those resulting in formation of an intra- HBond.) Here's
what I mean: small molecule studies lead to the idea that solute-water
HBonds are more favorable than solute-solute HBonds. However mutation
studies of proteins lead to the opposite conclusion: that intramolecular
HBonds are stabilizing. Of course, interpretation of the latter type of
experiment is complicated by matters of reference state and separability
of many effects.
There is a good paper by Radzicka and Wolfenden from which I can
grab the numbers you requested; surely we'll see that Ala is less soluble
in H20 (relative to the np solvent) than is glycine. What have you
learned with respect to your question of how E(P-P) relates to E(H-H)?
Rather, due to the uncertainty in reliably defining the three energies you
need I would suggest you define them simply. For example, in one simulation
you might use E(H-H)=2E(P-P), and in another E(H-H)=4(P-P). It seems that
E(H-P)=0 should be good enough for jazz, and that the case with E(H-H)
less favorable than E(P-P) probably doesn't need to be examined.
Is any of this helpful? So, what about Ken's model drives you to
numerically study it? And why are you diverging away from his definition of
the energies, which as I recall had E(H-H) nonzero, but the other energies
= 0?
Good luck. Hope it turns up something useful.
Shawn Huston