Re: [AMBER-Developers] Accuracy of the LCPO approximation

From: Ken Merz <>
Date: Thu, 17 Nov 2011 17:39:34 -0500


 That's how you had so much money while at PSU! Moonlighting!


On Nov 17, 2011, at 5:19 PM, Scott Le Grand wrote:

> Hey David, 1 ns of sampling barely begins to cover evaluating the accuracy
> of this approximation. In contrast, in my 1993 JCC paper, I randomly
> generated tens of thousands of uncorrelated conformations, then calculated
> their SASA with my algorithm, an *exact* but expensive algorithm out of
> Berkeley, and the Still approximation. Just like similar approaches like
> Kazunori Toma's Residues in a Sphere potential look right for native
> conformations, once you drift away from the native state, both of these
> approximations lose meaning. In the MolSurf case you see an overall
> correlation coefficient of ~0.3 which is essentially random (mine was 0.98
> or so). In fact, Clark Still himself offered me $14K to come up with
> derivatives for my method in order to replace his. I did so, but I'm not
> satisfied with their accuracy so I never published or took the money.
> So the question you have to ask yourself here is: do you feel lucky? Are
> you comfortable with using a potential term that is chomping at the bit to
> pull you away from the native state into the bizarro universe? I'd post
> the incriminating diagram but I'm at SC11 right now with no access to said
> paper. It's probably in your library though. Heck, you can probably
> download it.
> Scott
> On Thu, Nov 17, 2011 at 10:26 AM, David A Case <>wrote:
>> On Tue, Oct 04, 2011, Scott Le Grand wrote:
>>> As someone who wrote a *really* fast SASA approximation 18 years ago
>>> (basically Shrake and Rupley on steroids), here's my two cents.
>>> The Still et al. approximation at the heart of GBSA has a correlation
>>> coefficient of ~0.3 with the actual SASA. On the bright side, this
>>> approximation has a derivative.
>>> So if you're happy with some indeterminate analytic function of the
>> number
>>> of atoms surrounding a given atom as a surrogate for accurately
>> calculating
>>> the SASA, carry on... I'm not.
>> I'm moving this from the amber list to the amber-developers list. What
>> Scott
>> said didn't agree with what I remembered from a decade ago, so I asked Dan
>> to look into this question, and his initial results are attached.
>> Basically, although there are some real limitations with LCPO, a
>> description of it as an "indterminate analytic function" with low
>> correlation to the actual SASA isn't correct for this particular test.
>> Correlation coefficients of 0.86 and 0.99 are found in the two cases
>> looked at
>> here.
>> So: finding out more about what types of tests lead to the bad results
>> would
>> be useful, and it would also be nice to know about other approximations
>> that
>> we should consider.
>> ....dac
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Professor Kenneth M. Merz, Jr.
University of Florida Research Foundation Professor
Edmund H. Prominski Professor of Chemistry
Department of Chemistry
Quantum Theory Project
2328 New Physics Building
PO Box 118435
University of Florida
Gainesville, Florida 32611-8435


Phone: 352-392-6973
FAX: 352-392-8722
Cell: 814-360-0376

"The fundamental laws necessary for the mathematical treatment of a large part of physics and the whole of chemistry are thus completely known, and the difficulty lies only in the fact that application of these laws leads to equations that are too complex to be solved."

PAM Dirac, 1929

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Received on Thu Nov 17 2011 - 15:00:03 PST
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