DUDE - Revision history

Khtang at 20:35, 4 January 2019

2019-01-04T20:35:51Z

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	\|Developer = [[Shoichet Lab]]		\|Developer = [[Shoichet Lab]]
	\|Stable Version = [[DUDE]]		\|Stable Version = [[DUDE]]
	\|Programming Language = [[Python]], [[~~Perl~~]]		\|Programming Language = [[Python]], [[C-Shell]]
	\|Dependencies = [[JChem]], [[ChemAxon]]		\|Dependencies = [[JChem]], [[ChemAxon]]
	}}		}}

Khtang at 20:49, 3 January 2019

2019-01-03T20:49:51Z

← Older revision		Revision as of 20:49, 3 January 2019
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			{{Software_Infobox
			\|title = DUD-E
			\|image = Dud.jpg
			\|Paragigm = [[Docking]]
			\|Developer = [[Shoichet Lab]]
			\|Stable Version = [[DUDE]]
			\|Programming Language = [[Python]], [[Perl]]
			\|Dependencies = [[JChem]], [[ChemAxon]]
			}}

	This is the Wiki Page for '''DUD-E''' or (we like to call "DUDE"), a '''D'''irectory of '''U'''seful '''D'''ecoys - '''E'''nhanced. DUD-E is on the web at http://dude.docking.org.		This is the Wiki Page for '''DUD-E''' or (we like to call "DUDE"), a '''D'''irectory of '''U'''seful '''D'''ecoys - '''E'''nhanced. DUD-E is on the web at http://dude.docking.org.

Khtang: /* FAQ */

2018-12-20T22:30:34Z

FAQ

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	= FAQ =		= FAQ =
			DUD-E is a research tool which we have tried to make as useful and as correct as we know how. We will endeavor to put right any problems promptly, as best we can. We have also answered some questions below:
	== Q1. How duplicates are removed ==		== Q1. How duplicates are removed ==
	In the paper, you said "We then remove duplicate decoys from the ligand set by sorting decoys from		In the paper, you said "We then remove duplicate decoys from the ligand set by sorting decoys from

Khtang: /* A4. Why receptor.pdb is not the same as the PDB file */

2018-12-20T22:28:58Z

A4. Why receptor.pdb is not the same as the PDB file

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	I noticed that in the ace receptor.pdb structure some residues are missing compared to the original 3bkl.pdb. I am sure this won't influence docking results but nevertheless: is there a reason for this or just an artifact which happens in all big databases?		I noticed that in the ace receptor.pdb structure some residues are missing compared to the original 3bkl.pdb. I am sure this won't influence docking results but nevertheless: is there a reason for this or just an artifact which happens in all big databases?

	== A4. Why receptor.pdb is not the same as the PDB file ==		=== A4. Why receptor.pdb is not the same as the PDB file ===
	We know you can go to the PDB yourself and get the original structure. receptor.pdb shows you exactly, atom by atom, the model that we used for docking. In some cases, we have made some judgement calls to remove solvent, or even atoms distance from the binding site that are too far away to affect docking. For instance, we often remove atoms further than 25A away from the binding site. You are welcome to go back to the PDB to get the original structure.		We know you can go to the PDB yourself and get the original structure. receptor.pdb shows you exactly, atom by atom, the model that we used for docking. In some cases, we have made some judgement calls to remove solvent, or even atoms distance from the binding site that are too far away to affect docking. For instance, we often remove atoms further than 25A away from the binding site. You are welcome to go back to the PDB to get the original structure.




	= Community Feedback =		= Community Feedback =

Khtang: /* A3A. more about dups answered */

2018-12-20T22:28:43Z

A3A. more about dups answered

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	These have different protonation states of which only the bottom one is found in ZINC (http://zinc.docking.org/substance/39363328). Will these entries be cleaned up from the dataset (and possibly only the molecule in its physiological protonation state be kept) ? Or is this "by design" ? Isn't there the risk of having an "analog bias" effect if you keep both these molecules? I have attached the full list of duplicates found in the current decoy sets, just in case you are interested in following this further. (long file...)		These have different protonation states of which only the bottom one is found in ZINC (http://zinc.docking.org/substance/39363328). Will these entries be cleaned up from the dataset (and possibly only the molecule in its physiological protonation state be kept) ? Or is this "by design" ? Isn't there the risk of having an "analog bias" effect if you keep both these molecules? I have attached the full list of duplicates found in the current decoy sets, just in case you are interested in following this further. (long file...)

	== A3A. more about dups answered ==		=== A3A. more about dups answered ===
	For the decoys, we only ask ZINC for the single best representative at pH 7.05. So, when it gives more than one protonation state this is an error in ZINC itself, as the molecule had multiple versions of this "reference" state. The ones with the steriochemistry change are only that much more broken.		For the decoys, we only ask ZINC for the single best representative at pH 7.05. So, when it gives more than one protonation state this is an error in ZINC itself, as the molecule had multiple versions of this "reference" state. The ones with the steriochemistry change are only that much more broken.

	In the grand scheme, using your list there are only 1521 of these duplicates out of 1.4 million decoys (~ 0.1%), which actually means that ZINC has a much better error rate than in the past. My inclination is to leave it alone, but possibly document the duplicates as arising from errors in ZINC. If one wanted to fix this, the intermediate data is usually there in the raw ligand sets to fill in these decoys with others that don't have this problem (in the .filtered files).		In the grand scheme, using your list there are only 1521 of these duplicates out of 1.4 million decoys (~ 0.1%), which actually means that ZINC has a much better error rate than in the past. My inclination is to leave it alone, but possibly document the duplicates as arising from errors in ZINC. If one wanted to fix this, the intermediate data is usually there in the raw ligand sets to fill in these decoys with others that don't have this problem (in the .filtered files).


	== Q4. The receptor structure is not the same as in the PDB. Why? ==		== Q4. The receptor structure is not the same as in the PDB. Why? ==

Khtang: /* A3. Answers on duplicate IDs */

2018-12-20T22:28:25Z

A3. Answers on duplicate IDs

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	Where the same id refers to the different stereochemistry. My question is why was this design decision taken (to have both in the decoys file)? Perhaps a single entry with undefined stereochemistry at the differing position might be an alternative, or if two entries have different stereochemistry because they can be synthesised that way a suffix in the id would have been helpful "C02343192_1", "C02343192_2". Taking the representation in ZINC (in this case the bottom one) is also another possibility - but then where does the top one come from?		Where the same id refers to the different stereochemistry. My question is why was this design decision taken (to have both in the decoys file)? Perhaps a single entry with undefined stereochemistry at the differing position might be an alternative, or if two entries have different stereochemistry because they can be synthesised that way a suffix in the id would have been helpful "C02343192_1", "C02343192_2". Taking the representation in ZINC (in this case the bottom one) is also another possibility - but then where does the top one come from?

	=== ~~Q3A~~. Answers on duplicate IDs ===		=== A3. Answers on duplicate IDs ===
	The uniqueness of decoys is enforced at the level of protonation ids. At the time it was generated, there were 2 protomer ids for that zinc		The uniqueness of decoys is enforced at the level of protonation ids. At the time it was generated, there were 2 protomer ids for that zinc
	substance id.		substance id.

Khtang: /* Q3A. Answers on duplicate IDs */

2018-12-20T22:28:03Z

Q3A. Answers on duplicate IDs

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	Where the same id refers to the different stereochemistry. My question is why was this design decision taken (to have both in the decoys file)? Perhaps a single entry with undefined stereochemistry at the differing position might be an alternative, or if two entries have different stereochemistry because they can be synthesised that way a suffix in the id would have been helpful "C02343192_1", "C02343192_2". Taking the representation in ZINC (in this case the bottom one) is also another possibility - but then where does the top one come from?		Where the same id refers to the different stereochemistry. My question is why was this design decision taken (to have both in the decoys file)? Perhaps a single entry with undefined stereochemistry at the differing position might be an alternative, or if two entries have different stereochemistry because they can be synthesised that way a suffix in the id would have been helpful "C02343192_1", "C02343192_2". Taking the representation in ZINC (in this case the bottom one) is also another possibility - but then where does the top one come from?

	== Q3. Answers on duplicate IDs ==		=== Q3A. Answers on duplicate IDs ===
	The uniqueness of decoys is enforced at the level of protonation ids. At the time it was generated, there were 2 protomer ids for that zinc		The uniqueness of decoys is enforced at the level of protonation ids. At the time it was generated, there were 2 protomer ids for that zinc
	substance id.		substance id.
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	Only the second protomer remains now. So this was an error in ZINC that was later fixed. I expect these kinds of source errors to show up		Only the second protomer remains now. So this was an error in ZINC that was later fixed. I expect these kinds of source errors to show up
	in both ChEBML and ZINC.		in both ChEBML and ZINC.

	== Q3A. more about dups ==		== Q3A. more about dups ==

Khtang: /* A2. PDB receptor file residue labeling */

2018-12-20T22:26:30Z

A2. PDB receptor file residue labeling

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	* pde5a: Residues 653/4 are labeled as HIZ/DID where the original PDB file contains HIS/ASP.		* pde5a: Residues 653/4 are labeled as HIZ/DID where the original PDB file contains HIS/ASP.

	== A2. PDB receptor file residue labeling ==		=== A2. PDB receptor file residue labeling ===

	These are the actual preparations we used in DOCK itself. As explained in the paper, many of the targets have been enhanced to help docking performance. The non-standard residues most typically change the partial charges, which is used for metal-coordination and dipole "tarting". See docking/grids/prot.table.ambcrg.ambH in that targets directory for how the residue is being interpreted.		These are the actual preparations we used in DOCK itself. As explained in the paper, many of the targets have been enhanced to help docking performance. The non-standard residues most typically change the partial charges, which is used for metal-coordination and dipole "tarting". See docking/grids/prot.table.ambcrg.ambH in that targets directory for how the residue is being interpreted.
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	The funky names help to make our manual intervention explicit and transparent.		The funky names help to make our manual intervention explicit and transparent.



	== Q3. More on duplicate IDs ==		== Q3. More on duplicate IDs ==

Khtang: /* A1. Duplicate removal procedure */

2018-12-20T22:26:14Z

A1. Duplicate removal procedure

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	similarity. Please explain!		similarity. Please explain!

	== A1. Duplicate removal procedure ==		===A1. Duplicate removal procedure ===
	Decoys are uniquely identified by their ZINC protonation ids. We		Decoys are uniquely identified by their ZINC protonation ids. We
	ensure that a particular protonation id (prot_id) is only assigned to		ensure that a particular protonation id (prot_id) is only assigned to

Khtang at 22:24, 20 December 2018

2018-12-20T22:24:02Z

← Older revision		Revision as of 22:24, 20 December 2018
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	\|}		\|}
	</div>		</div>
	</div>		</div>
			==Cite DUD-E==
			To cite DUD-E, please reference Mysinger MM, Carchia M, Irwin JJ, Shoichet BK J. Med. Chem., 2012, Jul 5. [http://pubs.acs.org/doi/10.1021/jm300687e DOI 10.1021/jm300687e] . You may also wish to cite the original version of DUD, Huang, Shoichet and Irwin, J. Med. Chem., 2006, 49(23), 6789-6801. [http://pubs.acs.org/doi/abs/10.1021/jm0608356 DOI 10.1021/jm0608356].

	= Detailed file documentation =		= Detailed file documentation =