Subject: Re: CCL:low barrier hydrogen bonds

From: Arno Papazyan <[email-masked]>
Date: Mon, 18 May 1998 12:33:22 -0700 (PDT)

Sorry for jumping into the LBHB thread so late. I have been away for a
CECAM workshop, and now I am writing this message from a yet another 
country.

In order to ask meaningful questions on LBHBs, we first have to know what
they are. Perhaps surprisingly, not all "low-barrier" hydrogen bonds are
"low-barrier hydrogen bonds" !!
The original LBHB hypothesis in enzyme catalysis was not clear about the
distinction between "regular" or "ordinary" HBs and LBHBs, other than the
fact that LBHBs had a low barrier for proton motion in the HB. However,
since the barrier itself is basically irrelevant to enzyme catalysis other
than as a rough correlator of bond energy (but not even as an indicator of
relative stabilities of alternative HB+environment configurations),
and using the bond energy or relative stability would be circular, one has
to define LBHBs in terms of their source of stabilization. We can
decompose an HB into its "electrostatic" and "covalent" contributions. An
"ordinary" HB (OHB) has both electrostatic and covalent components, although
it can be reasonably modelled by classical force fields by dumping everything
into electrostatic parameters. An OHB can be neutral or charged. A charged 
HB is often stronger than the neutral variety, and this difference can often 
be explained electrostatically. So, usually there is nothing unusual or non-"ordinary" about a strong, short HB (very often with little or no barrier to proton motion). The only true distinction would come from an unusually large
"covalent" or "purely quantum mechanical" contribution to the bond energy.
Thus one should understand that most (if not the vast majority) of the so-called "LBHB"s are plain, old, mundane, ordinary HBs!  ;-)  And therefore somewhat
modellable by classical force fields to the same extent that they have been until now ;-) Of course, why anyone would get excited over an already-well-known 
effect in enzyme catalysis is another matter! ;-)
As for catching anomalously high covalent contributions, obviously something
quantum mechanical should be done. My humble opinion on this is that a well-calibrated Empirical Valence Bond approach would be a natural choice. A super-
duper hyper-expensive "traditional" quantum calculation need not be used
directly, but rather as a calibration for the EVB description, which may then be used quite reliably to your hearts content. This makes catching a true LBHB 
"almost" accessible to force-field simulations.
To end this note, let me re-emphasize that without distinguishing charged
HBs from LBHBs, and without representing the solvation of the system accurately,
One should not even try working on this question.
Regards to all,
Arno Papazyan