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Evolutionary algorithm [message #465] Tue, 12 February 2019 17:20 Go to next message
pc419714@ohio.edu is currently offline  pc419714@ohio.edu
Messages: 18
Registered: February 2019
Junior Member
When I use the evolutionary algorithm and select a scaffold it says the selected structures are left untouched. However the scaffolds are mutated. Is there any way to just mutate the R groups only and leave the skeletons unchanged? We are doing this to conform with certain criteria.

Thanks for this amazing software!
Re: Evolutionary algorithm [message #466 is a reply to message #465] Tue, 12 February 2019 18:40 Go to previous messageGo to next message
thomas is currently offline  thomas
Messages: 208
Registered: June 2014
Senior Member
When you define the first generation of molecules, then you may double click any of them to open the structure in the structure editor. Use the lasso tool and select the scaffold, which should not be touched. When selected, all scaffold atoms and bonds should be drawn in red. Then close the editor. In the list of first generation molecules, the unmutable scaffolds should still be drawn in red. When starting the evolution, these atoms and bonds won't be changed in any way. I just checked that this is still working. See example image...

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[Updated on: Tue, 12 February 2019 18:41]

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Re: Evolutionary algorithm [message #475 is a reply to message #466] Wed, 13 February 2019 23:05 Go to previous messageGo to next message
pc419714@ohio.edu is currently offline  pc419714@ohio.edu
Messages: 18
Registered: February 2019
Junior Member
Thank you so much!
Re: Evolutionary algorithm [message #476 is a reply to message #475] Thu, 14 February 2019 04:28 Go to previous messageGo to next message
pc419714@ohio.edu is currently offline  pc419714@ohio.edu
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Registered: February 2019
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Also, I am wondering about clustering using flexophores. This measure is supposed to give you a measure of biological activity..... Does this mean that it predicts binding to specific proteins? Will it tell you what a given molecule will bind if I generated the flexophores and then clustered? It supposedly takes a lot of time and memory so I wanted to make sure before I did it. I just wanted to know which kinases my molecules bind, so I selected find similar compounds in file for a large data set of known kinase inhibitors and found which ones were similar. I did not use the flexophores though. Would the flexophores give me more information on the function of my molecules than skelspheres would? Thanks again!
Re: Evolutionary algorithm [message #484 is a reply to message #476] Thu, 07 March 2019 16:25 Go to previous messageGo to next message
thomas is currently offline  thomas
Messages: 208
Registered: June 2014
Senior Member
When you have a few active molecules on a given target and intend to search a large compound collection for similar compounds in order to find more potential active ones, then the fastest approach is to use chemical(=graph) similarity of some kind, e.g. the SkeletonSpheres descriptor. Very similar compounds often have similar activities. The drawback of this approach is that this won't do scaffold hopping, which mean that you won't find structures with a substantially different structure core or substitution pattern. The idea of the flexophore (https://pubs.acs.org/doi/abs/10.1021/ci700359jWink addresses this issue. It was designed to compare the representative conformer sets of two molecules concerning their protein-binding potential. It classifies atoms that may contribute to binding using PDB statistics. The flexophore considers molecules similar, if they contains atoms that have similar binding behaviour to protein atoms if these atoms' relative 3D orientations are also similar. Depending on the conformational flexibility of individual molecules and the target you may achieve a significantly higher hit rate compared to random or diverse selection, if you preselect screening candidates by flexophore similarity.
Re: Evolutionary algorithm [message #495 is a reply to message #484] Thu, 14 March 2019 22:08 Go to previous message
pc419714@ohio.edu is currently offline  pc419714@ohio.edu
Messages: 18
Registered: February 2019
Junior Member
thanks
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