Re: [AMBER] accuracy of FEW free energy calculation

From: Jiri Sponer <>
Date: Sat, 20 Jun 2015 19:38:09 +0200 (MEST)

I think it has been quite interesting discussion and I in fact I would
appreciate to see more such say "controversial" discussions.
In general I see that year by year papers are getting on average more and
more "inflated".
Publication of negative and unpopular
results is definitely NOT rewarded in contemporary science,
I would even tell it is risky.

I need to emphasize that I do not want to judge that specific problem due
to lack of experience.


On Sat, 20 Jun 2015, Jason Swails wrote:

> Date: Sat, 20 Jun 2015 12:29:10 -0400
> From: Jason Swails <>
> Reply-To: AMBER Mailing List <>
> To: AMBER Mailing List <>
> Subject: Re: [AMBER] accuracy of FEW free energy calculation
> 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
> direction).
> ​Good luck,
> Jason
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
> _______________________________________________
> AMBER mailing list

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Received on Sat Jun 20 2015 - 11:00:02 PDT
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