Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Marco Stenta]

Hi Folks,
We are building a tool that generates libraries of compounds based on a
list of reactants and a set of compatible reactants, and allows selection
of the products.
 We define the process as "product-based reactant selection" from an old
paper (at the end of the day we need to make these compounds!)
We call the product "Library Design Tool" considering the Design composed
of generation (enumeration) and selection phases.
Our people got used to the term reaction-based enumeration (but I am not
sure if they still distinguish from R-Group-Enumeration), virtual products
and the like, but in hindsight in silico synthesis ... definitely not bad.

Cheeers,
m

Il giorno ven 25 set 2020 alle ore 15:26 Ivan Tubert-Brohman <
ivan.tubert-broh...@schrodinger.com> ha scritto:

> We use "reaction-based enumeration" to distinguish it from "R-group
> enumeration". Both are types of virtual library enumeration.
>
> R-group enumeration allows you to attach any R-group anywhere. It is
> simple and fast but you can easily create implausible (or hard to
> synthesize) molecules if you are not careful.
>
> Reaction-based enumeration at least guarantees that you already have
> reactants with the right functional groups in the right places, and if you
> make your reactions sophisticated enough you can even check for other
> disqualifying conditions such as interfering functional groups.
>
> Of course in a context where it is not immediately obvious that you are
> talking about doing it on a computer, I suppose something along the lines
> of "virtual reaction-based enumeration" might make sense.
>
> Best,
> Ivan
>
>
> On Fri, Sep 25, 2020 at 4:26 AM Thomas Strunz 
> wrote:
>
>> Hi Brian,
>>
>> commercial tools usually use the term "reaction-based enumeration" or
>> "reaction-based library design".
>>
>> Best Regards,
>>
>> Thomas
>>
>> --
>> *Von:* Bennion, Brian via Rdkit-discuss <
>> rdkit-discuss@lists.sourceforge.net>
>> *Gesendet:* Freitag, 25. September 2020 07:19
>> *An:* RDKit Discuss 
>> *Betreff:* [Rdkit-discuss] proper technical term for generating virtual
>> compounds with rdkit and smarts
>>
>> hello
>>
>> I have a paper in review and is intended for a large audience that has
>> synthetic chemists, biologist and comp chem.
>> One reviewer had issues with the term in-silico syntheses.
>> I used rdkit and smarts reactions to generate large libraries of
>> compounds for our research project.  Is there a better term to use?  I feel
>> "chemical enumeration" is just as foreign.
>>
>> The abstract is below.
>>
>> The current standard treatment for organophosphate poisoning primarily
>> relies on the use of small molecule-based oximes that can efficiently
>> restore acetylcholinesterase (AChE) activity.  Despite their efficacy in
>> reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is
>> primarily limited to the peripheral nervous system (PNS) and, thus,
>> provides no protection to the central nervous system (CNS).  This lack
>> of action in the CNS stems from the ionic nature of the drugs; they
>> cannot cross the blood-brain barrier (BBB) to access to any nerve
>> agent-inhibited AChE therein.  In this report, we present a small
>> molecule oxime, called LLNL-02, that can diffuse across the BBB for
>> reactivation of nerve agent-inhibited AChE in the CNS.  Our 
>> candidate-development
>> approach utilizes a combination of parallel chemical and in - silico
>> syntheses, computational modeling, and a battery of detailed in vitro
>> and in vivo assessments that have identified LLNL-02 as a top CNS-active 
>> candidate
>> against nerve agent poisoning.   Additional experiments to determine acute
>> and chronic  toxicity as required for regulatory approval are ongoing.
>>
>> ___
>> Rdkit-discuss mailing list
>> Rdkit-discuss@lists.sourceforge.net
>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
> ___
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Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Ivan Tubert-Brohman]

We use "reaction-based enumeration" to distinguish it from "R-group
enumeration". Both are types of virtual library enumeration.

R-group enumeration allows you to attach any R-group anywhere. It is simple
and fast but you can easily create implausible (or hard to synthesize)
molecules if you are not careful.

Reaction-based enumeration at least guarantees that you already have
reactants with the right functional groups in the right places, and if you
make your reactions sophisticated enough you can even check for other
disqualifying conditions such as interfering functional groups.

Of course in a context where it is not immediately obvious that you are
talking about doing it on a computer, I suppose something along the lines
of "virtual reaction-based enumeration" might make sense.

Best,
Ivan


On Fri, Sep 25, 2020 at 4:26 AM Thomas Strunz  wrote:

> Hi Brian,
>
> commercial tools usually use the term "reaction-based enumeration" or
> "reaction-based library design".
>
> Best Regards,
>
> Thomas
>
> --
> *Von:* Bennion, Brian via Rdkit-discuss <
> rdkit-discuss@lists.sourceforge.net>
> *Gesendet:* Freitag, 25. September 2020 07:19
> *An:* RDKit Discuss 
> *Betreff:* [Rdkit-discuss] proper technical term for generating virtual
> compounds with rdkit and smarts
>
> hello
>
> I have a paper in review and is intended for a large audience that has
> synthetic chemists, biologist and comp chem.
> One reviewer had issues with the term in-silico syntheses.
> I used rdkit and smarts reactions to generate large libraries of compounds
> for our research project.  Is there a better term to use?  I feel "chemical
> enumeration" is just as foreign.
>
> The abstract is below.
>
> The current standard treatment for organophosphate poisoning primarily
> relies on the use of small molecule-based oximes that can efficiently
> restore acetylcholinesterase (AChE) activity.  Despite their efficacy in
> reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is
> primarily limited to the peripheral nervous system (PNS) and, thus,
> provides no protection to the central nervous system (CNS).  This lack of
> action in the CNS stems from the ionic nature of the drugs; they cannot
> cross the blood-brain barrier (BBB) to access to any nerve
> agent-inhibited AChE therein.  In this report, we present a small
> molecule oxime, called LLNL-02, that can diffuse across the BBB for
> reactivation of nerve agent-inhibited AChE in the CNS.  Our 
> candidate-development
> approach utilizes a combination of parallel chemical and in - silico
> syntheses, computational modeling, and a battery of detailed in vitro and in
> vivo assessments that have identified LLNL-02 as a top CNS-active candidate
> against nerve agent poisoning.   Additional experiments to determine acute
> and chronic  toxicity as required for regulatory approval are ongoing.
>
> ___
> Rdkit-discuss mailing list
> Rdkit-discuss@lists.sourceforge.net
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
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Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Thomas Strunz]

Hi Brian,

commercial tools usually use the term "reaction-based enumeration" or 
"reaction-based library design".

Best Regards,

Thomas


Von: Bennion, Brian via Rdkit-discuss 
Gesendet: Freitag, 25. September 2020 07:19
An: RDKit Discuss 
Betreff: [Rdkit-discuss] proper technical term for generating virtual compounds 
with rdkit and smarts

hello

I have a paper in review and is intended for a large audience that has 
synthetic chemists, biologist and comp chem.
One reviewer had issues with the term in-silico syntheses.
I used rdkit and smarts reactions to generate large libraries of compounds for 
our research project.  Is there a better term to use?  I feel "chemical 
enumeration" is just as foreign.

The abstract is below.


The current standard treatment for organophosphate poisoning primarily relies 
on the use of small molecule-based oximes that can efficiently restore 
acetylcholinesterase (AChE) activity.  Despite their efficacy in reactivating 
AChE, the action of drugs like 2-pralidoxime (2-PAM) is primarily limited to 
the peripheral nervous system (PNS) and, thus, provides no protection to the 
central nervous system (CNS).  This lack of action in the CNS stems from the 
ionic nature of the drugs; they cannot cross the blood-brain barrier (BBB) to 
access to any nerve agent-inhibited AChE therein.  In this report, we present a 
small molecule oxime, called LLNL-02, that can diffuse across the BBB for 
reactivation of nerve agent-inhibited AChE in the CNS.  Our 
candidate-development approach utilizes a combination of parallel chemical and 
in - silico syntheses, computational modeling, and a battery of detailed in 
vitro and in vivo assessments that have identified LLNL-02 as a top CNS-active 
candidate against nerve agent poisoning.   Additional experiments to determine 
acute and chronic  toxicity as required for regulatory approval are ongoing.

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Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Rafal Roszak]

Hello Brian,

On Fri, 25 Sep 2020 05:19:14 +
"Bennion, Brian via Rdkit-discuss"
 wrote:

> I have a paper in review and is intended for a large audience that has 
> synthetic chemists, biologist and comp chem.
> One reviewer had issues with the term in-silico syntheses.
> I used rdkit and smarts reactions to generate large libraries of compounds 
> for our research project.  Is there a better term to use?  I feel "chemical 
> enumeration" is just as foreign.

It seems there is no nomenclature for this. I agree with Greg that
is silico synthesis is nice wording. However it is commonly
used, yet. I this our job to popularize this term :)
In our recent paper 
https://science.sciencemag.org/content/369/6511/eaaw1955.full
we use terms:
1. computer-assisted organic synthesis
2. computer-generated reaction networks 
3. computer-predicted synthesis 
4. computer-designed plan

I think computer-predicted/computer-proposed reaction/compounds/paths should be 
undertandable for broad audience.

Best,

Rafal


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Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Stephen Roughley via Rdkit-discuss]

I recall the first time I heard the term was in a project meeting in
RiboTargets back in around 1999/2000.  One of our modelling group used it
after hearing discussion of results of in vitro and in vivo studies being
discussed.  My recollection is that there was a certain amount of amusement
at the time as it was a term none of us had heard previously, along with
some friendly discussion as to whether in fact wet chemistry was performed
in silico, given that glass is made from silicates.  I wonder if anyone has
come across an earlier use of the term?

Steve


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<#DAB4FAD8-2DD7-40BB-A1B8-4E2AA1F9FDF2>

On Fri, 25 Sep 2020 at 08:09, Hannes Loeffler 
wrote:

> Without your more detailled explanation of what that term specifically
> means I was wondering too at first.  But then I did the most obvious
> thing: search for it online and found
>
> https://scholar.google.com/scholar?q=%22in+silico+synthesis%22=en_sdt=0_vis=1=scholart
> .  Looks to me other people use the term and in similar fashion as you
> too
>
> On Fri, 25 Sep 2020 at 06:21, Bennion, Brian via Rdkit-discuss
>  wrote:
> >
> > hello
> >
> > I have a paper in review and is intended for a large audience that has
> synthetic chemists, biologist and comp chem.
> > One reviewer had issues with the term in-silico syntheses.
> > I used rdkit and smarts reactions to generate large libraries of
> compounds for our research project.  Is there a better term to use?  I feel
> "chemical enumeration" is just as foreign.
> >
> > The abstract is below.
> >
> > The current standard treatment for organophosphate poisoning primarily
> relies on the use of small molecule-based oximes that can efficiently
> restore acetylcholinesterase (AChE) activity.  Despite their efficacy in
> reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is
> primarily limited to the peripheral nervous system (PNS) and, thus,
> provides no protection to the central nervous system (CNS).  This lack of
> action in the CNS stems from the ionic nature of the drugs; they cannot
> cross the blood-brain barrier (BBB) to access to any nerve agent-inhibited
> AChE therein.  In this report, we present a small molecule oxime, called
> LLNL-02, that can diffuse across the BBB for reactivation of nerve
> agent-inhibited AChE in the CNS.  Our candidate-development approach
> utilizes a combination of parallel chemical and in - silico syntheses,
> computational modeling, and a battery of detailed in vitro and in vivo
> assessments that have identified LLNL-02 as a top CNS-active candidate
> against nerve agent poisoning.   Additional experiments to determine acute
> and chronic  toxicity as required for regulatory approval are ongoing.
> >
> >
> > ___
> > Rdkit-discuss mailing list
> > Rdkit-discuss@lists.sourceforge.net
> > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>
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Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Hannes Loeffler]

Without your more detailled explanation of what that term specifically
means I was wondering too at first.  But then I did the most obvious
thing: search for it online and found
https://scholar.google.com/scholar?q=%22in+silico+synthesis%22=en_sdt=0_vis=1=scholart
.  Looks to me other people use the term and in similar fashion as you
too

On Fri, 25 Sep 2020 at 06:21, Bennion, Brian via Rdkit-discuss
 wrote:
>
> hello
>
> I have a paper in review and is intended for a large audience that has 
> synthetic chemists, biologist and comp chem.
> One reviewer had issues with the term in-silico syntheses.
> I used rdkit and smarts reactions to generate large libraries of compounds 
> for our research project.  Is there a better term to use?  I feel "chemical 
> enumeration" is just as foreign.
>
> The abstract is below.
>
> The current standard treatment for organophosphate poisoning primarily relies 
> on the use of small molecule-based oximes that can efficiently restore 
> acetylcholinesterase (AChE) activity.  Despite their efficacy in reactivating 
> AChE, the action of drugs like 2-pralidoxime (2-PAM) is primarily limited to 
> the peripheral nervous system (PNS) and, thus, provides no protection to the 
> central nervous system (CNS).  This lack of action in the CNS stems from the 
> ionic nature of the drugs; they cannot cross the blood-brain barrier (BBB) to 
> access to any nerve agent-inhibited AChE therein.  In this report, we present 
> a small molecule oxime, called LLNL-02, that can diffuse across the BBB for 
> reactivation of nerve agent-inhibited AChE in the CNS.  Our 
> candidate-development approach utilizes a combination of parallel chemical 
> and in - silico syntheses, computational modeling, and a battery of detailed 
> in vitro and in vivo assessments that have identified LLNL-02 as a top 
> CNS-active candidate against nerve agent poisoning.   Additional experiments 
> to determine acute and chronic  toxicity as required for regulatory approval 
> are ongoing.
>
>
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> Rdkit-discuss@lists.sourceforge.net
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Re: [Rdkit-discuss] proper technical term for generating virtual compounds with rdkit and smarts

[Greg Landrum]

I actually like *in silico* synthesis - though I don't think I've seen it
before - but I can imagine a chemist finding it objectionable.
I would probably use "virtual library enumeration"

-greg

On Fri, Sep 25, 2020 at 7:21 AM Bennion, Brian via Rdkit-discuss <
rdkit-discuss@lists.sourceforge.net> wrote:

> hello
>
> I have a paper in review and is intended for a large audience that has
> synthetic chemists, biologist and comp chem.
> One reviewer had issues with the term in-silico syntheses.
> I used rdkit and smarts reactions to generate large libraries of compounds
> for our research project.  Is there a better term to use?  I feel "chemical
> enumeration" is just as foreign.
>
> The abstract is below.
>
> The current standard treatment for organophosphate poisoning primarily
> relies on the use of small molecule-based oximes that can efficiently
> restore acetylcholinesterase (AChE) activity.  Despite their efficacy in
> reactivating AChE, the action of drugs like 2-pralidoxime (2-PAM) is
> primarily limited to the peripheral nervous system (PNS) and, thus,
> provides no protection to the central nervous system (CNS).  This lack of
> action in the CNS stems from the ionic nature of the drugs; they cannot
> cross the blood-brain barrier (BBB) to access to any nerve
> agent-inhibited AChE therein.  In this report, we present a small
> molecule oxime, called LLNL-02, that can diffuse across the BBB for
> reactivation of nerve agent-inhibited AChE in the CNS.  Our 
> candidate-development
> approach utilizes a combination of parallel chemical and in - silico
> syntheses, computational modeling, and a battery of detailed in vitro and in
> vivo assessments that have identified LLNL-02 as a top CNS-active candidate
> against nerve agent poisoning.   Additional experiments to determine acute
> and chronic  toxicity as required for regulatory approval are ongoing.
>
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