Synthesia - Revision history

Iamkaant: /* How to create this tree? */

2022-10-11T17:43:11Z

How to create this tree?

← Older revision		Revision as of 17:43, 11 October 2022
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	* Sci-Finder Retrosynthesis. Exports results in .pdf only, but at least you can copy compound SMILES from the Retrosynthesis Plan, just click on the structure and select "Substance Detail".		* Sci-Finder Retrosynthesis. Exports results in .pdf only, but at least you can copy compound SMILES from the Retrosynthesis Plan, just click on the structure and select "Substance Detail".
	* IBM RXN https://rxn.res.ibm.com/. Based on machine-extracted patent reactions. You have to manually select reactions for each step.		* IBM RXN https://rxn.res.ibm.com/. Based on machine-extracted patent reactions. You have to manually select reactions for each step.
			* Spaya AI https://spaya.ai.

	In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.		In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.

Iamkaant: added retrosynthesis route generation by IBM RXN

2022-08-11T18:57:24Z

added retrosynthesis route generation by IBM RXN

← Older revision		Revision as of 18:57, 11 August 2022
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	* Reaxys Retrosynthesis tool (was not able to find a root for granisetron though, seems to use only published procedures)		* Reaxys Retrosynthesis tool (was not able to find a root for granisetron though, seems to use only published procedures)
	* Sci-Finder Retrosynthesis. Exports results in .pdf only, but at least you can copy compound SMILES from the Retrosynthesis Plan, just click on the structure and select "Substance Detail".		* Sci-Finder Retrosynthesis. Exports results in .pdf only, but at least you can copy compound SMILES from the Retrosynthesis Plan, just click on the structure and select "Substance Detail".
			* IBM RXN https://rxn.res.ibm.com/. Based on machine-extracted patent reactions. You have to manually select reactions for each step.

	In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.		In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.

Iamkaant at 21:11, 3 August 2022

2022-08-03T21:11:54Z

← Older revision		Revision as of 21:11, 3 August 2022
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	In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.		In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.


	=== Configuration file ===		=== Configuration file ===

Iamkaant: added retrosynthesis route generation tools

2022-08-03T21:10:09Z

added retrosynthesis route generation tools

← Older revision		Revision as of 21:10, 3 August 2022
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	]		]
	}		}
	</syntaxhighlight>How to create this tree?		</syntaxhighlight>
			==== How to create this tree? ====
			* If only one stage needed -- just write manually.
			* The authors used open-source ML tool AiZynthFinder: https://jcheminf.biomedcentral.com/articles/10.1186/s13321-020-00472-1, https://github.com/MolecularAI/aizynthfinder
			* Reaxys Retrosynthesis tool (was not able to find a root for granisetron though, seems to use only published procedures)
			* Sci-Finder Retrosynthesis. Exports results in .pdf only, but at least you can copy compound SMILES from the Retrosynthesis Plan, just click on the structure and select "Substance Detail".

			In any case, except for one stage synthesis, I would recommend consulting a synthetic chemist before creating analogs.


	=== Configuration file ===		=== Configuration file ===

Iamkaant at 20:49, 3 August 2022

2022-08-03T20:49:07Z

← Older revision		Revision as of 20:49, 3 August 2022
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	<code>--allLeaves</code> -- '''very important''': without it you will only get suitable BBs and not final structures. The README says: ''Set this parameter to true if all chemical leaf nodes should be open for exchange. Either this parameter or the option allChemicals must be set or the nodeId parameter must be specified''.		<code>--allLeaves</code> -- '''very important''': without it you will only get suitable BBs and not final structures. The README says: ''Set this parameter to true if all chemical leaf nodes should be open for exchange. Either this parameter or the option allChemicals must be set or the nodeId parameter must be specified''.

	<code>--useECFP</code> -- filter analogs by ECFP. 4 parameter values are expected:		<code>--useECFP</code> -- filter analogs by ECFP. 4 parameter values are expected: <Integer> <String> <Integer> <Integer> The first number equals the appended number of the FCFP. The second string parameters specifies the similarity measure method for a fingerprint comparison. Options are 'tanimoto', 'cosine', 'hamming', 'euclidean', 'dice.' The third number specifies the minimum threshold value for the similarity fingerprint comparison and the fourth number specifies the maximum threshold value.

	<Integer> <String> <Integer> <Integer>

	The first number equals the appended number of the FCFP. The second string parameters specifies the similarity measure method for a fingerprint comparison. Options are 'tanimoto', 'cosine', 'hamming', 'euclidean', 'dice.' The third number specifies the minimum threshold value for the similarity fingerprint comparison and the fourth number specifies the maximum threshold value.

	This command executed on Gimel returns 511 analogs of granisetron in 1'56" from 436K BBs.		This command executed on Gimel returns 511 analogs of granisetron in 1'56" from 436K BBs.

Iamkaant at 20:48, 3 August 2022

2022-08-03T20:48:39Z

← Older revision		Revision as of 20:48, 3 August 2022
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	The first number equals the appended number of the FCFP. The second string parameters specifies the similarity measure method for a fingerprint comparison. Options are 'tanimoto', 'cosine', 'hamming', 'euclidean', 'dice.' The third number specifies the minimum threshold value for the similarity fingerprint comparison and the fourth number specifies the maximum threshold value.		The first number equals the appended number of the FCFP. The second string parameters specifies the similarity measure method for a fingerprint comparison. Options are 'tanimoto', 'cosine', 'hamming', 'euclidean', 'dice.' The third number specifies the minimum threshold value for the similarity fingerprint comparison and the fourth number specifies the maximum threshold value.

			This command executed on Gimel returns 511 analogs of granisetron in 1'56" from 436K BBs.

	=== Conclusion ===		=== Conclusion ===

Iamkaant at 20:46, 3 August 2022

2022-08-03T20:46:45Z

← Older revision		Revision as of 20:46, 3 August 2022
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	Pros of Synthesia — flexibility, multistage reactions of virtually any complexity and number of stages, fine-tuning of analog properties (No. of aromatic rings, halogens, cations, logP…).		Pros of Synthesia — flexibility, multistage reactions of virtually any complexity and number of stages, fine-tuning of analog properties (No. of aromatic rings, halogens, cations, logP…).

	Cons — closed sources, steep learning curve, need to create retrosynthetic trees for each compound.		Cons — closed sources, licensing on a per-year basis, steep learning curve, need to create retrosynthetic trees for each compound.

	My resume at the moment — may be interesting to look into given access to a synthetic chemistry group.		My resume at the moment — may be interesting to look into given access to a synthetic chemistry group.

Iamkaant: Created page with "
Synthesia is a command-line tool that uses an entire retrosynthetic route as a guide pathway to generate optimized structural analogues of a lead compound without..."

2022-08-03T20:44:49Z

Created page with "<blockquote>Synthesia is a command-line tool that uses an entire retrosynthetic route as a guide pathway to generate optimized structural analogues of a lead compound without..."

New page

<blockquote>Synthesia is a command-line tool that uses an entire retrosynthetic route as a guide pathway to generate optimized structural analogues of a lead compound without compromising the synthesizability of the structure. The users has the ability to guide the structural modifications in a desired direction by specifying structural constraints.</blockquote>Original publication: https://pubs.acs.org/doi/10.1021/acs.jcim.2c00246

Website: https://software.zbh.uni-hamburg.de/customers/tools

== Installation ==
To obtain the license, you need to register and get your account approved. Then login to the website, click on Synthesia and "Download the license file". Your license key is inside the file, it looks like <code>AAAAAAAliFQAAAAU2eM8ZjTTELGD3LzxBgt3/1DGaW4=</code>. Copy the license key from the file, download and unpack the program and run the command:

<code>./synthesia --license <your_license_here></code>

My installation is in <code>/mnt/nfs/exa/work/ak87/UCSF/SynthI/SYNTHESIA/synthesia_1.0.0</code>

== Running ==
To run the program, you need:

# a retrosynthetic tree and
# a library of building blocks ("<code>SMILES Name</code>", no preprocessing needed).

The tool returns analogs of a target molecule synthesizable by the given route from given BBs. The analogs may be filtered by 29 different parameters (see SI or README.md file):

# Extended-Connectivity Fingerprints (ECFP)
# Functional-Class Fingerprints (FCFP)
# Connected Subgraph Fingerprints (CSFP)
# Largest Ring
# Largest Ringsystem
# Molecular Weight
# Number of Hydrogen-Bond Acceptors
# Number of Anions
# Number of Aromatic Atoms
# Number of Aromatic Rings
# Number of Aromatic Ringsystems
# Number of Cations
# Number of Hydrogen-Bond Donors
# Number of Halogens
# Number of Non-Hydrogen Atoms
# Number of Hetero Atoms
# Number of Hydrophobic Points
# Number of Inorganic Atoms
# Number of Lipinski Donors
# Number of Nitrogens and Oxygens
# Number of Non-Hydrogen Bonds
# Number of Rings
# Number of Ringsystems
# Number of Rotatable Bonds
# LogP-Value
# Total Charge
# Topological Polar Surface Area (TPSA)
# Volume
# Matching SMARTSS3 pattern. Either inclusion or exclusion

=== Retrosynthetic tree ===
This is a .json file that describes all steps needed to synthesize the molecule in question and starting reagents. The steps are encoded in SMARTS. Each reaction node should contain reaction SMARTS + SMILES of the product. The tree for [https://zinc15.docking.org/substances/ZINC000000000347/ granisetron] synthesis via amidation is shown below.<syntaxhighlight lang="json">
{
"smiles": "CN1C2CCCC1CC(C2)NC(=O)c1nn(C)c2ccccc12",
"is_chemical": true,
"children":
[
{
"smiles": "CN1C2CCCC1CC(C2)NC(=O)c1nn(C)c2ccccc12",
"is_reaction": true,
"smartsPattern": "[#7:1].[#8]-[#6:2](=O)>>[#7:1]-[#6:2](=O)",
"children":
[
{
"smiles": "Cn1nc(C(O)=O)c2ccccc12",
"is_chemical": true,
"children": []
},
{
"smiles": "CN1C2CCCC1CC(N)C2",
"is_chemical": true,
"children": []
}
]
}
]
}
</syntaxhighlight>How to create this tree?

=== Configuration file ===
<blockquote>All additional settings of Synthesia can be specified in a configuration file. This file is optional and the user does not have to use it. If both the configuration file as well as command line parameters are used to define parameters, the settings parsed via command line overwrite settings defined in the configuration file. The configuration file has to be in valid standard JSON format. An example configuration file is bundled with Synthesia.</blockquote>So far I've been using only command line parameters.

=== Running ===
<code>./synthesia --inputStructures ../../Enamine-BB/2022-03_Chemspace_Building_Blocks_noRU_SMILES.smiles --retroSynTree amide_tree.json --output amide_out-ecfp.json --threads 4 --verbosity 5 --allLeaves --useECFP 2 tanimoto 0.6 1.0</code>

<code>--inputStructures</code> -- a library of BBs

<code>--retroSynTree</code> -- self-explanatory

<code>--output</code> -- output .json file

<code>--threads</code> -- Number of threads used for parallelization.

<code>--allLeaves</code> -- '''very important''': without it you will only get suitable BBs and not final structures. The README says: ''Set this parameter to true if all chemical leaf nodes should be open for exchange. Either this parameter or the option allChemicals must be set or the nodeId parameter must be specified''.

<code>--useECFP</code> -- filter analogs by ECFP. 4 parameter values are expected:

<Integer> <String> <Integer> <Integer>

The first number equals the appended number of the FCFP. The second string parameters specifies the similarity measure method for a fingerprint comparison. Options are 'tanimoto', 'cosine', 'hamming', 'euclidean', 'dice.' The third number specifies the minimum threshold value for the similarity fingerprint comparison and the fourth number specifies the maximum threshold value.

=== Conclusion ===
Pros of Synthesia — flexibility, multistage reactions of virtually any complexity and number of stages, fine-tuning of analog properties (No. of aromatic rings, halogens, cations, logP…).

Cons — closed sources, steep learning curve, need to create retrosynthetic trees for each compound.

My resume at the moment — may be interesting to look into given access to a synthetic chemistry group.