Re: [AMBER] accuracy of FEW free energy calculation

From: Jason Swails <>
Date: Sat, 20 Jun 2015 12:29:10 -0400

On Sat, Jun 20, 2015 at 1:08 AM, Albert <> wrote:

> Hi Ross:
> thanks a lot for such honest comments.
> I just knew it, they were using many cheating and tricks in that JACS paper
> and made such beautiful story to the outside. As far as I know, Schrodinger
> is going to sell this product to many big pharmaceutical company with
> bloody price that you cannot imagine. However, after asthmatically testing,
> most of them dump it which I could expect in advance.
> For science part, the Schrodinger FEP Mapper solvate the protein/ligand
> complex in a 5A TIP3P box and then produce 5ns MD in all for ligand. It
> assigned OPLS-2.1, which claimed to be the most accurate FF for small
> molecules, for the system. The job is primarily running on GPU. I don't
> know whether this will lead to the converge of the calculation or not for
> Alchemical FEP. Meanwhile, in this mapper stuff, if one provide
> experimental date in the input file, they will use some mathematical
> function to "MAKE" you final results correlate the data one provided at the
> beginning. Probably that's one of the key reason why the plot in that JACS
> paper looks so perfect. If this is the case, then the plot is totally a
> fake and unreliable, it is a totally commercial strategy.

​I think this is a little pessimistic. If you are having trouble
correlating your results in the same way that Schrodinger did in their
paper, you should contact them for help. They wouldn't stay in business if
their methods were based on cheating and could only achieve good results on
hand-tuned retrospective studies. I haven't read the paper yet, and it's
entirely possible that the method doesn't work as well as the paper would
suggest, but I know and respect a lot of the scientists that work at
Schrodinger. Your accusations are at odds with my experience with them.
So I would suggest trying to reconcile why your simulations are not
yielding similar results to theirs rather than simply chalking it up to
scientific dishonesty and corporate deceit.

Another comment I'll make is that papers are subject to peer review which,
while not a perfect system, has been quite effective at pushing forward
good science and filtering out the bad (at least eventually). By contrast,
none of our emails in which we answer questions here are subject to peer
review, so I would suggest treating our responses with at least as much
(and usually more) skepticism than, for instance, JACS papers. This isn't
to say you should blindly accept anything people publish in JACS, but you
shouldn't consider what we say here to be any more reliable (treat them as
tips to help give you a fuller picture and/or get you pointed in the right

​Good luck,

Jason M. Swails
Rutgers University
Postdoctoral Researcher
AMBER mailing list
Received on Sat Jun 20 2015 - 09:30:02 PDT
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