Planar amide bonds next to aromatic systems

Hi,





I'm using MarvinSketch 4.0.5 on OS 10.3.9


I've got a problem generating planar amide bonds where the nitrogen is next to an aromatic system.





If the nitrogen is connected to a non-aromatic atom then the amide bond is planar, but if the atom the nitrogen is connected to is aromatic then the bond becomes non-planar.





I attach an example of each. I'm drawing these in MarvinSketch, adding explicit hydrogens and cleaning in 3D (Fine Build)





Thanks

Hi,





Your structures are not easy cases for conformational analysis with a simple MM method, like the Dreiding force-filed used in the current version of MarvinSketch. I optimized your "non-planar" structure using a quantum chemical method and got the attached structure. Also, after simply optimizing your structure with more strict optimization criteria I've got the "more-planar" structure.


Strict optimization was done by using molconvert:





molconvert -3:c01Eo103 sdf non-planar.mol >more-planar.sdf





Unfortunately, all molecular mechanics forcefields have limitations, considerably more accurate results can only be achieved using more sophisticated (and also more CPU demanding), e.g. quantum chemical, methods.





I hope my answer was useful.





Best wishes,





Ödön

msleeman wrote:

Hi, I'm using MarvinSketch 4.0.5 on OS 10.3.9 I've got a problem generating planar amide bonds where the nitrogen is next to an aromatic system. If the nitrogen is connected to a non-aromatic atom then the amide bond is planar, but if the atom the nitrogen is connected to is aromatic then the bond becomes non-planar. I attach an example of each. I'm drawing these in MarvinSketch, adding explicit hydrogens and cleaning in 3D (Fine Build) Thanks

Hi Ödön,





Thank you for your very helpful reply.





Would you suggest using the more strict optimisation setting for generating structures generally or are there some drawbacks to them?





Is there a way to use these more strict optimisation rules from within MarvinSketch?





What would be the molconvert command line equivalents of the MarvinSketch clean 3D (fine build) and clean 3D (optimize)?





Thanks,





Mark

ofarkas wrote:

Hi, Your structures are not easy cases for conformational analysis with a simple MM method, like the Dreiding force-filed used in the current version of MarvinSketch. I optimized your "non-planar" structure using a quantum chemical method and got the attached structure. Also, after simply optimizing your structure with more strict optimization criteria I've got the "more-planar" structure. Strict optimization was done by using molconvert: molconvert -3:c01Eo103 sdf non-planar.mol >more-planar.sdf Unfortunately, all molecular mechanics forcefields have limitations, considerably more accurate results can only be achieved using more sophisticated (and also more CPU demanding), e.g. quantum chemical, methods. I hope my answer was useful. Best wishes, Ödön msleeman wrote: Hi, I'm using MarvinSketch 4.0.5 on OS 10.3.9 I've got a problem generating planar amide bonds where the nitrogen is next to an aromatic system. If the nitrogen is connected to a non-aromatic atom then the amide bond is planar, but if the atom the nitrogen is connected to is aromatic then the bond becomes non-planar. I attach an example of each. I'm drawing these in MarvinSketch, adding explicit hydrogens and cleaning in 3D (Fine Build) Thanks

Hi Mark,





Using strict optimization always help getting more accurate results but may increase the required CPU time considerably.





Using "o103" as option (instead of o1 in the following examples) will result in strict optimization.





The molconvert equivalents of the GUI options are:


Fast: -3:S{fast}


Fine: -3:S{fine}


Build or optimize: -3:c01o1S{fine}


Optimize: -3:c2o1





Best wishes,





Ödön

msleeman wrote:

Hi Ödön, Thank you for your very helpful reply. Would you suggest using the more strict optimisation setting for generating structures generally or are there some drawbacks to them? Is there a way to use these more strict optimisation rules from within MarvinSketch? What would be the molconvert command line equivalents of the MarvinSketch clean 3D (fine build) and clean 3D (optimize)? Thanks, Mark