Running ChemSTEP - Revision history

Kholland at 22:54, 7 May 2026

2026-05-07T22:54:15Z

← Older revision		Revision as of 22:54, 7 May 2026
Line 29:		Line 29:
	\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/22B/22M_seeds.sdi</code>		\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/22B/22M_seeds.sdi</code>
	\|-		\|-
	\| 72B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/72B/~~72B_seeds~~.sdi</code>		\| 72B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/72B/72M_seeds.sdi</code>
	\|}		\|}

Kholland at 22:49, 7 May 2026

2026-05-07T22:49:52Z

← Older revision		Revision as of 22:49, 7 May 2026
Line 140:		Line 140:
	\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/22B/22B_fplib.pickle</code>		\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/22B/22B_fplib.pickle</code>
	\|-		\|-
	\| 72B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/72B/~~72B_seeds~~.~~sdi~~</code>		\| 72B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/72B/72B_fplib.pickle</code>
	\|}		\|}

Kholland at 22:44, 7 May 2026

2026-05-07T22:44:50Z

← Older revision		Revision as of 22:44, 7 May 2026
Line 1:		Line 1:
	last update: ~~dec 16 2025~~ katie. current ver = ~~0.3.1.5~~ (~~automatic resubmission of failed SGE jobs~~).		last update: may 07 2026 katie. current ver = 03 (integrated IFP).

	ChemSTEP (Chemical Space Traversal and Exploration Procedure) is an open-source, transparent acceleration algorithm for molecular docking capable of dealing with virtual libraries of several trillion compounds. This wiki page is a guide for BKS lab members to run ChemSTEP on Wynton HPC, using a ~~drug-like~~ subset of ZINC (22B) or 13.3B library from Enamine REAL. '''for detailed instructions on the 13B space, see 'Running ChemSTEP on the 13B space' wiki page'''. For more general use directions, please refer to [ChemSTEP Read-the-Docs].		ChemSTEP (Chemical Space Traversal and Exploration Procedure) is an open-source, transparent acceleration algorithm for molecular docking capable of dealing with virtual libraries of several trillion compounds. This wiki page is a guide for BKS lab members to run ChemSTEP on Wynton HPC, using a subset of ZINC (22B or 72B) or 13.3B library from Enamine REAL. '''for detailed instructions on the 13B space, see 'Running ChemSTEP on the 13B space' wiki page'''. For more general use directions, please refer to [ChemSTEP Read-the-Docs].

	At a high-level, ChemSTEP is an iterative process that identifies molecules from the larger virtual library to prioritize for docking. First, we identify a random sample of the total library (termed "seed set", round zero) and dock those molecules to the target of interest. From this seed set, we can calculate total-library pProp values (-log rank percentages) and the number of "virtual hits" in the total library (high-scoring molecules). ChemSTEP will identify a set of maximally diverse molecules that score above the desired pProp threshold ("beacons") from the seed set. These beacons guide prioritization, where molecules chosen and output by ChemSTEP are close in chemical space to the beacons. Prioritized molecules are then built, docked, and returned to ChemSTEP for a second round of prioritization. This process is iterated until you reach desired virtual hit recovery, or you are no longer recovering virtual hits.		At a high-level, ChemSTEP is an iterative process that identifies molecules from the larger virtual library to prioritize for docking. First, we identify a random sample of the total library (termed "seed set", round zero) and dock those molecules to the target of interest. From this seed set, we can calculate total-library pProp values (-log rank percentages) and the number of "virtual hits" in the total library (high-scoring molecules). ChemSTEP will identify a set of maximally diverse molecules that score above the desired pProp threshold ("beacons") from the seed set. These beacons guide prioritization, where molecules chosen and output by ChemSTEP are close in chemical space to the beacons. Prioritized molecules are then built, docked, and returned to ChemSTEP for a second round of prioritization. This process is iterated until you reach desired virtual hit recovery, or you are no longer recovering virtual hits.
Line 8:		Line 8:
	= Running ChemSTEP (Auto DOCK and Build) =		= Running ChemSTEP (Auto DOCK and Build) =

	ChemSTEP is configured to run on Wynton with libraries of '''13B''' and '''~~22B~~'''. This page covers the full workflow for running ChemSTEP with automatic submission of docking and building jobs.		ChemSTEP is configured to run on Wynton with libraries of '''13B''', '''22B''' (HAC 17-26, cLogP <= 3.5), and '''72B''' (HAC4-49, cLogP <=4.0). This page covers the full workflow for running ChemSTEP with automatic submission of docking and building jobs.

	__TOC__		__TOC__
Line 15:		Line 15:

	<pre>		<pre>
	source /wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/bin/activate		source /wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/bin/activate
	</pre>		</pre>

Line 25:		Line 25:
	! Library !! Path		! Library !! Path
	\|-		\|-
	\| 13B \|\| <code>/wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/libraries/13B/13M_seeds.sdi</code>		\| 13B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/13B/13M_seeds.wynton.sdi</code>
	\|-		\|-
	\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/libraries/22B/22M_seeds.sdi</code>		\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/22B/22M_seeds.sdi</code>
			\|-
			\| 72B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/72B/72B_seeds.sdi</code>
	\|}		\|}

Line 36:		Line 38:
	Once docking is complete, run the following from the directory '''one level above''' your docking output (<code>MOLECULES_DIR_TO_BIND</code>).		Once docking is complete, run the following from the directory '''one level above''' your docking output (<code>MOLECULES_DIR_TO_BIND</code>).

	'''22B library:'''		'''22B/72B library:'''
	<pre>		<pre>
	python /wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/get_scores.py 0		python /wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/get_scores.py 0
	</pre>		</pre>

	'''13B library:'''		'''13B library:'''
	<pre>		<pre>
	python /wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/~~get_scores_13B~~.py 0 MOL		python /wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/get_scores.py 0 MOL
	</pre>		</pre>

	{{Note\|You must specify the molecule ID prefix for the 13B library (<code>MOL</code>)~~.}}~~		Note: You must specify the molecule ID prefix for the 13B library (<code>MOL</code>)

	Verify that <code>scores_round_0.txt</code> was correctly written:		Verify that <code>scores_round_0.txt</code> was correctly written:
Line 58:		Line 60:

	<pre>		<pre>
	python /wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/convert_scores_to_npy.py 0 <mol_id_prefix>		python /wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/convert_scores_to_npy.py 0 <mol_id_prefix>
	</pre>		</pre>

Line 114:		Line 116:
	\| <code>hit_pprop</code> \|\| Defines a "virtual hit." pProp = −log(rank%) within the total library score distribution. E.g., pProp 4 in 13B space ≈ top 0.01% (~1.3M molecules); pProp 5 ≈ 0.001% (~132K). The seed set should contain at least 10<sup>(pProp+2)</sup> molecules.		\| <code>hit_pprop</code> \|\| Defines a "virtual hit." pProp = −log(rank%) within the total library score distribution. E.g., pProp 4 in 13B space ≈ top 0.01% (~1.3M molecules); pProp 5 ≈ 0.001% (~132K). The seed set should contain at least 10<sup>(pProp+2)</sup> molecules.
	\|-		\|-
	\| <code>n_docked_per_round</code> \|\| Number of molecules prioritized per round. All must be built and docked between rounds. Too many slows throughput and may reduce diversity; too few slows virtual hit recovery.		\| <code>n_docked_per_round</code> \|\| Number of molecules prioritized per round. All must be built and docked between rounds. Too many slows throughput and may reduce diversity; too few slows virtual hit recovery. Recommended: 1-2 million
	\|-		\|-
	\| <code>max_beacons</code> \|\| Diverse, well-scoring molecules used to guide prioritization. All molecules above the pProp threshold are candidates. Too many ~~reduces~~ inter-beacon diversity; too few ~~hinders~~ space exploration. Fewer beacons than specified may be assigned if insufficient molecules clear the threshold.		\| <code>max_beacons</code> \|\| Diverse, well-scoring molecules used to guide prioritization. All molecules above the pProp threshold are candidates. Too many reduce inter-beacon diversity; too few hinder space exploration. Fewer beacons than specified may be assigned if an insufficient number of molecules clear the threshold. Recommended: 100
	\|-		\|-
	\| <code>bundle_size</code> \|\| In auto docking mode, number of molecules submitted as a single build job.		\| <code>bundle_size</code> \|\| In auto docking mode, number of molecules submitted as a single build job.
Line 134:		Line 136:
	! Library !! Path		! Library !! Path
	\|-		\|-
	\| 13B \|\| <code>/wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/libraries/13B/boltz_fplib.pickle</code>		\| 13B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/13B/boltz_fplib.pickle</code>
	\|-		\|-
	\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/libraries/22B/22B_fplib.pickle</code>		\| 22B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/22B/22B_fplib.pickle</code>
			\|-
			\| 72B \|\| <code>/wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/libraries/72B/72B_seeds.sdi</code>
	\|}		\|}

Line 225:		Line 229:

	<pre>		<pre>
	python /wynton/group/bks/work/shared/kholland/~~chemstep_auto_v02~~/scripts/get_beacon_smiles.py /path/to/library/pickle chemstep_algo.log		python /wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/get_beacon_smiles.py /path/to/library/pickle chemstep_algo.log
	</pre>		</pre>

	Use the library pickle path from [[#7. Edit run_chemstep.py\|Step 7]].		Use the library pickle path from [[#7. Edit run_chemstep.py\|Step 7]].

	== 11. Get Poses After Docking ==		== 11. Plot Hit Recovery ==

			In your ChemSTEP directory containing <code>chemstep_algo.log</code> and score files,
			<pre>
			bash /wynton/group/bks/work/shared/kholland/chemstep_auto_v03_ifp/v03_ifp/scripts/submit_hit_recovery.sh
			</pre>

			== 12. Get Poses After Docking ==

	Make a list of <code>test.mol2.gz.0</code> files from docking:		Make a list of <code>test.mol2.gz.0</code> files from docking:

Kholland at 16:53, 16 March 2026

2026-03-16T16:53:01Z

Show changes

Kholland at 20:29, 9 February 2026

2026-02-09T20:29:14Z

← Older revision		Revision as of 20:29, 9 February 2026
Line 21:		Line 21:

	'''1. Source ChemSTEP virtual environment on Wynton'''		'''1. Source ChemSTEP virtual environment on Wynton'''
	source /wynton/group/bks/work/shared/kholland/~~chemstep_auto~~/bin/activate		source /wynton/group/bks/work/shared/kholland/chemstep_auto_v02/bin/activate

Kholland at 22:43, 12 January 2026

2026-01-12T22:43:34Z

← Older revision		Revision as of 22:43, 12 January 2026
Line 70:		Line 70:

	'''5. Enter into or make a directory to run ChemSTEP in. Copy in necessary files for initiating ChemSTEP: params.txt, run_chemstep.py and launch_chemstep_as_job.sh. Copy in your score and indices numpy files as well, which should be in your docking directory.'''		'''5. Enter into or make a directory to run ChemSTEP in. Copy in necessary files for initiating ChemSTEP: params.txt, run_chemstep.py and launch_chemstep_as_job.sh. Copy in your score and indices numpy files as well, which should be in your docking directory.'''
	cp /wynton/group/bks/work/shared/kholland/chemstep_auto/params.txt .		cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/params.txt .
	cp /wynton/group/bks/work/shared/kholland/chemstep_auto/run_chemstep.py .		cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/run_chemstep.py .
	cp /wynton/group/bks/work/shared/kholland/chemstep_auto/launch_chemstep_as_job.sh .		cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/launch_chemstep_as_job.sh .

Kholland at 19:41, 16 December 2025

2025-12-16T19:41:19Z

← Older revision		Revision as of 19:41, 16 December 2025
Line 149:		Line 149:
	cp /wynton/group/bks/work/shared/chemstep_13B_scripts_tutorial/launch_chemstep_iterative.sh .		cp /wynton/group/bks/work/shared/chemstep_13B_scripts_tutorial/launch_chemstep_iterative.sh .

	'''10. Run ChemSTEP'''		'''11. Run ChemSTEP'''
	qsub launch_chemstep_as_job.sh [round number]		qsub launch_chemstep_as_job.sh [round number]

Kholland at 19:30, 16 December 2025

2025-12-16T19:30:53Z

← Older revision		Revision as of 19:30, 16 December 2025
Line 25:		Line 25:

	'''2. Copy seed-set SDI file into your docking directory'''		'''2. Copy seed-set SDI file into your docking directory'''
	This directory should already contain your dockfiles, with INDOCK parameters set to your liking. In this step, we are copying in a split database index file (SDI) containing paths to bundles of db2 files. This seed set contains ~~100~~ million molecules sampled randomly from the total virtual library, currently ~~1.1 trillion~~ molecules.		This directory should already contain your dockfiles, with INDOCK parameters set to your liking. In this step, we are copying in a split database index file (SDI) containing paths to bundles of db2 files. This seed set contains 92 million molecules sampled randomly from the total virtual library, currently 96 billion molecules (ZINC).
	cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/96M_seeds.wynton.sdi .		cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/96M_seeds.wynton.sdi .
	cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/rebuilt_seeds.wynton.sdi .		cp /wynton/group/bks/work/shared/kholland/chemstep_auto/scripts/rebuilt_seeds.wynton.sdi .

Kholland at 19:27, 16 December 2025

2025-12-16T19:27:09Z

← Older revision		Revision as of 19:27, 16 December 2025
Line 102:		Line 102:


	'''7. Edit run_chemstep.py''' ~~note that the default parameters when copying over run_chemstep.py invoke the automatic building and docking pipeline.~~		'''7. Edit run_chemstep.py'''

	There are several configurable parameters that can be passed when first calling the CSAlgo object:		There are several configurable parameters that can be passed when first calling the CSAlgo object:
Line 113:		Line 113:
	more optional parameters to come.		more optional parameters to come.

	At this time, we strongly suggest running ChemSTEP as a job array with 16 ~~or 32~~ CPU slots requested. The number of cores must be specified when calling CSAlgo (in run_chemstep.py) and the SGE wrapper(launch_chemstep_as_job.sh).		At this time, we strongly suggest running ChemSTEP as a job array with 8 or 16 CPU slots requested. The number of cores must be specified when calling CSAlgo (in run_chemstep.py) and the SGE wrapper(launch_chemstep_as_job.sh).

Kholland at 19:26, 16 December 2025

2025-12-16T19:26:00Z

← Older revision		Revision as of 19:26, 16 December 2025
Line 1:		Line 1:
	last update: dec 15 2025 katie. current ver = 0.3.1.5 (automatic resubmission of failed SGE jobs).		last update: dec 16 2025 katie. current ver = 0.3.1.5 (automatic resubmission of failed SGE jobs).

	ChemSTEP (Chemical Space Traversal and Exploration Procedure) is an open-source, transparent acceleration algorithm for molecular docking capable of dealing with virtual libraries of several trillion compounds. This wiki page is a guide for BKS lab members to run ChemSTEP on Wynton HPC, using the current version of ZINC library (96B) or 13.3B library from Enamine REAL. '''for detailed instructions on the 13B space, see 'Running ChemSTEP on the 13B space' wiki page'''. For more general use directions, please refer to [ChemSTEP Read-the-Docs].		ChemSTEP (Chemical Space Traversal and Exploration Procedure) is an open-source, transparent acceleration algorithm for molecular docking capable of dealing with virtual libraries of several trillion compounds. This wiki page is a guide for BKS lab members to run ChemSTEP on Wynton HPC, using the current version of ZINC library (96B) or 13.3B library from Enamine REAL. '''for detailed instructions on the 13B space, see 'Running ChemSTEP on the 13B space' wiki page'''. For more general use directions, please refer to [ChemSTEP Read-the-Docs].
Line 102:		Line 102:


	'''7. Edit run_chemstep.py'''		'''7. Edit run_chemstep.py''' note that the default parameters when copying over run_chemstep.py invoke the automatic building and docking pipeline.

	There are several configurable parameters that can be passed when first calling the CSAlgo object:		There are several configurable parameters that can be passed when first calling the CSAlgo object:

	'''docking_method=''' setting this to "auto" will set up and run iterative rounds of building, docking, and running ChemSTEP. If you choose the auto method, be sure to update the full path to your dockfiles in run_chemstep.py and check that all INDOCK parameters are set to your liking. NOTE: docking method is set to auto if you copy in the scripts as outlined above. Change if desired!!!!!		'''docking_method=''' setting this to "auto" will set up and run iterative rounds of building, docking, and running ChemSTEP. If you choose the auto method, be sure to update the full path to your dockfiles in run_chemstep.py and check that all INDOCK parameters are set to your liking. NOTE: docking method is set to auto if you copy in the scripts as outlined above. Change if desired!!!!!


	'''min_td_search=''' setting this parameter will ~~establich~~ a minimum-tanimoto distance "zone" around each beacon for prioritization. For example, setting a min_td_search=0.3 will require that each prioritized molecule be greater than 0.3 Td from each beacon.		'''min_td_search=''' setting this parameter will establish a minimum-tanimoto distance "zone" around each beacon for prioritization. For example, setting a min_td_search=0.3 will require that each prioritized molecule be greater than 0.3 Td from each beacon.

	more optional parameters to come.		more optional parameters to come.