Reference LogP / PSA

> Dear all,
>
> I have a few questions about method used for descriptors calculations
> in openbabel.
>
> What are the methods used for LogP, PSA and MR calculation? (a
> reference could be enough, I didn't found this information on
> openbabel website).
>
> Is amide bond considered as a rotatable bond? I think so after reading
> the "bool IsRotor( )" description, but I prefer to be sure :)
>
> And can anybody decode the smarts strings posted by Noel (thanks!)
> describing HBD and NHA?
>
> HBD: [!#6;!H0]
> I understand the !#6 as "not carbon", but that's all... What does the
> zero do? Does it mean a hydrogen attached to any atom excepted carbon?
>
> HBA: [$([$([#8,#16]);!$(*=N~O);!$(*~N=O);X1,X2]),$([#7;v3;!$([nH]);!$(*(-a)-a)])]
> I would like a text version for that too :)
>
> Many thanks!
> Regards,
> Pascal
>
> -------------------------------------------------------------------------
> This SF.net email is sponsored by: Microsoft
> Defy all challenges. Microsoft(R) Visual Studio 2005.
> http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/
> _______________________________________________
> OpenBabel-discuss mailing list
> [hidden email]
> https://lists.sourceforge.net/lists/listinfo/openbabel-discuss
>

> Dear all,
>
> I have a few questions about method used for descriptors calculations
> in openbabel.
>
> What are the methods used for LogP, PSA and MR calculation? (a
> reference could be enough, I didn't found this information on
> openbabel website).
>
> Is amide bond considered as a rotatable bond? I think so after reading
> the "bool IsRotor( )" description, but I prefer to be sure :)
>
> And can anybody decode the smarts strings posted by Noel (thanks!)
> describing HBD and NHA?
>
> HBD: [!#6;!H0]
> I understand the !#6 as "not carbon", but that's all... What does the
> zero do? Does it mean a hydrogen attached to any atom excepted carbon?
>
> HBA: [$([$([#8,#16]);!$(*=N~O);!$(*~N=O);X1,X2]),$([#7;v3;!$([nH]);!$(*(-a)-a)])]
> I would like a text version for that too :)
>
> Many thanks!
> Regards,
> Pascal
>
> -------------------------------------------------------------------------
> This SF.net email is sponsored by: Microsoft
> Defy all challenges. Microsoft(R) Visual Studio 2005.
> http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/
> _______________________________________________
> OpenBabel-discuss mailing list
> [hidden email]
> https://lists.sourceforge.net/lists/listinfo/openbabel-discuss
>

> In relation to the other descriptors, see the following email on this list:
> http://www.nabble.com/logP-calculation-tf4193856.html
>
> (I find Nabble very useful for searching the mailing list - note to
> self: add this to the documentation as well as these descriptor
> references)
>
> Regarding "Is amide bond considered as a rotatable bond?". Uh...this
> requires looking at the code, which says:
>
>   bool OBBond::IsRotor()
>   {
>     return(_bgn->GetHvyValence() > 1 && _end->GetHvyValence() > 1 &&
>            _order == 1 && !IsInRing() && _bgn->GetHyb() != 1 &&
>            _end->GetHyb() != 1);
>   }
>
> Hmmm....in an amide bond, I expect the hybridisation of the C and N to
> be 2 (i.e. sp2), so it looks like the expression above evaluates to
> True. I think this is a bug. Can some of the C++ guys comment?
> Presumably adding a check for amide is possible, and also desirable?
>
> Noel
>
> On 11/09/2007, Pascal Muller <[hidden email]> wrote:
> > Dear all,
> >
> > I have a few questions about method used for descriptors calculations
> > in openbabel.
> >
> > What are the methods used for LogP, PSA and MR calculation? (a
> > reference could be enough, I didn't found this information on
> > openbabel website).
> >
> > Is amide bond considered as a rotatable bond? I think so after reading
> > the "bool IsRotor( )" description, but I prefer to be sure :)
> >
> > And can anybody decode the smarts strings posted by Noel (thanks!)
> > describing HBD and NHA?
> >
> > HBD: [!#6;!H0]
> > I understand the !#6 as "not carbon", but that's all... What does the
> > zero do? Does it mean a hydrogen attached to any atom excepted carbon?
> >
> > HBA: [$([$([#8,#16]);!$(*=N~O);!$(*~N=O);X1,X2]),$([#7;v3;!$([nH]);!$(*(-a)-a)])]
> > I would like a text version for that too :)
> >
> > Many thanks!
> > Regards,
> > Pascal
> >
> > -------------------------------------------------------------------------
> > This SF.net email is sponsored by: Microsoft
> > Defy all challenges. Microsoft(R) Visual Studio 2005.
> > http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/
> > _______________________________________________
> > OpenBabel-discuss mailing list
> > [hidden email]
> > https://lists.sourceforge.net/lists/listinfo/openbabel-discuss
> >
>

> Hi,
>
> Sorry, the mail is a bit long. 3 parts: LogP/PSA, HBD/HBA and RB. I
> need help mainly on smarts reading.
>
> [LogP]
> > There is some discussion of this in the comments in my blog article:
> > http://baoilleach.blogspot.com/2007/07/pybel-hack-that-sd-file.html
>
> Right, thanks. I found the reference for LogP in
> http://openbabel.svn.sourceforge.net/viewvc/openbabel/openbabel/trunk/data/logp.txt?view=markup
>
> What for PSA?
>
>
> [HBD/HBA]
>
> > Maybe someone here can comment further. If you are using these
> > strings,
>
> I would like to, I must compute descriptors for my library.
>
> > you could do us all a big favour by checking the references
> > and letting us know if everything is OK according to your own chemical
> > knowledge.
>
> Like GMC2007 commented on your blog, I prefer to use Lipinski's
> definition of donor/acceptor for library descriptors. However, if
> Lipinski HBA definition include or exclude e.g. amide or aromatic
> nitrogen, I don't know. I must check.
>
> Here
> http://openbabel.svn.sourceforge.net/viewvc/openbabel/openbabel/trunk/src/smartsdescriptors.cpp?view=markup#l_57
> we have
>
> HBD: "[!#6;!H0]","Number of Hydrogen Bond Donors (JoelLib)");
> HBA1: "[$([!#6;+0]);!$([F,Cl,Br,I]);!$([o,s,nX3]);!$([Nv5,Pv5,Sv4,Sv6])]",
> "Number of Hydrogen Bond Acceptors 1 (JoelLib)");
> HBA2: "[$([$([#8,#16]);!$(*=N~O);!$(*~N=O);X1,X2]),$([#7;v3;!$([nH]);!$(*(-a)-a)])]",
> "Number of Hydrogen Bond Acceptors 2 (JoelLib)");
>
> Does the first part of HBA2 means "any oxygen (excepted in nitroso or
> oxyme) or sulfur atom with one or 2 connections"? (It's the X1,X2 part
> which is annoying me).
>
> On Daylight website we can read:
> Hydrogen-bond donor.
> [!$([#6,H0,-,-2,-3])]
> "A H-bond donor is a non-negatively charged heteroatom with at least one H"
> [!H0;#7,#8,#9]
> "Must have an N-H bond, an O-H bond, or a F-H bond"
>
> I'll use HBD [#7,#8;!H0] (any nitrogen or oxygen with at least one
> attached hydrogen) for my purpose.
> (By the way, is P-H a HBD?)
>
>
> Still from Daylight site:
>  Hydrogen-bond acceptor
>     [!$([#6,F,Cl,Br,I,o,s,nX3,#7v5,#15v5,#16v4,#16v6,*+1,*+2,*+3])]
>     A H-bond acceptor is a heteroatom with no positive charge, note
> that negatively charged oxygen or sulphur are included. Excluded are
> halogens, including F, heteroaromatic oxygen, sulphur and pyrrole N.
> Higher oxidation levels of N,P,S are excluded. Note P(III) is currentl
> y included.
>
> Well, amide nitrogen and e.g. Phe-NH2 are considered HBA with that
> definition, and the same in JoelLib HBA1 and HBA2, isn't it?
>
> Assuming all 3-connected nitrogen next to sp2 or sp carbon smarts is
> [NX3][c,C&X3,C&X2] like written in the comment in Noel's blog post
> (does this smarts means : a nitrogen atom, with 3 neighbours, bound to
> an aromatic carbon, or to a carbon with 3 neighbours, or to a carbon
> with 2 neighbours?)
> the smarts for HBA should be (?):
> [ !$([#6,F ... +3,]);  !$([NX3][c,C&X3,C&X2])  ]
>
> OK, better to do some tests to see if I understood these unreadable smarts...
>
>
> [Amide / rotatable bond]
>
> > Regarding "Is amide bond considered as a rotatable bond?". Uh...this
> > requires looking at the code, which says:
>
>  bool OBBond::IsRotor()
>  {
>    return(_bgn->GetHvyValence() > 1 && _end->GetHvyValence() > 1 &&
>           _order == 1 && !IsInRing() && _bgn->GetHyb() != 1 &&
>           _end->GetHyb() != 1);
>  }
>
> I'm neither a C++ reader...
> _bgn->GetHvyValence() > 1 && _end->GetHvyValence() > 1
> Both atoms must not be hydrogen...
>
> _order == 1
> ...and the bond must be simple...
>
> !IsInRing()
> ... and is not included in a ring...
>
> bgn->GetHyb() != 1 &&_end->GetHyb() != 1)
> ... and both atom must not... well, what are the values for hybridization?
>
> > Hmmm....in an amide bond, I expect the hybridization of the C and N to
> > be 2 (i.e. sp2), so it looks like the expression above evaluates to
> > True. I think this is a bug. Can some of the C++ guys comment?
> > Presumably adding a check for amide is possible, and also desirable?
>
> In the "rule of 3" definition I found (and I'm interested in for the
> moment), which include RB, the amide bond is not considered as
> rotatable - I agree with that.
> I would go either for considering amide bond as not rotatable, either
> giving the choice (amide bond optionally rotatable / not rotatable by
> default) to the user.
> But of course that's would only corresponding to my personnal usage.
>
> > Since OpenBabel is not the only Open Source cheminformatics toolkit,
> > we can compare and contrast....
> >
> > The CDK uses a SMARTS pattern for determining the number of rotatable
> > bonds as described here:
> > http://cheminfo.informatics.indiana.edu/~rguha/code/java/nightly/api/org/openscience/cdk/qsar/descriptors/molecular/RotatableBondsCountDescriptor.html
> >
> > It would be interesting and useful to determine all those cases where
> > this value disagrees with OpenBabel...
>
> Following multiple links I got finally to
> http://www.daylight.com/dayhtml_tutorials/languages/smarts/smarts_examples.html#ROTATE
>
> Rotatable bond   [!$(*#*)&!D1]-!@[!$(*#*)&!D1]
> "An atom which is not triply bonded and not one-connected i.e.terminal
> connected by a single non-ring bond to and equivalent atom."
>
> Consider amide bond as rotatable as far I understand the definition -
> didn't even give a try for that smarts :)
>
> Regards,
> Pascal
>
> -------------------------------------------------------------------------
> This SF.net email is sponsored by: Microsoft
> Defy all challenges. Microsoft(R) Visual Studio 2005.
> http://clk.atdmt.com/MRT/go/vse0120000070mrt/direct/01/
> _______________________________________________
> OpenBabel-discuss mailing list
> [hidden email]
> https://lists.sourceforge.net/lists/listinfo/openbabel-discuss
>

> Here
> http://openbabel.svn.sourceforge.net/viewvc/openbabel/openbabel/ 
> trunk/src/smartsdescriptors.cpp?view=markup#l_57
> we have
>
> HBD: "[!#6;!H0]","Number of Hydrogen Bond Donors (JoelLib)");
> HBA1: "[$([!#6;+0]);!$([F,Cl,Br,I]);!$([o,s,nX3]);!$
> ([Nv5,Pv5,Sv4,Sv6])]",
> "Number of Hydrogen Bond Acceptors 1 (JoelLib)");
> HBA2: "[$([$([#8,#16]);!$(*=N~O);!$(*~N=O);X1,X2]),$([#7;v3;!$
> ([nH]);!$(*(-a)-a)])]",
> "Number of Hydrogen Bond Acceptors 2 (JoelLib)");

> Following multiple links I got finally to
> http://www.daylight.com/dayhtml_tutorials/languages/smarts/ 
> smarts_examples.html#ROTATE
>
> Rotatable bond   [!$(*#*)&!D1]-!@[!$(*#*)&!D1]
> "An atom which is not triply bonded and not one-connected i.e.terminal
> connected by a single non-ring bond to and equivalent atom."
>
> Consider amide bond as rotatable as far I understand the definition -
> didn't even give a try for that smarts :)