DOCKovalent cysteine inhibitor design tutorial - Revision history

Frodo: asdf

2023-03-20T22:23:15Z

asdf

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	From Schrondinger covalent datasets 38 systems		From Schrondinger covalent datasets 38 systems


			[[Category:Covalent]]

Xiaobo wan at 01:02, 19 July 2018

2018-07-19T01:02:24Z

← Older revision		Revision as of 01:02, 19 July 2018
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	save the linker viewdock state: P		save the linker viewdock state: P
	perl step0-filter_by_the_chimera.pl pdb to extract the final poses		perl step0-filter_by_the_chimera.pl pdb to extract the final poses

			==Step 8 8-pose-benchmark-systems==
			From paper 1 the https://code.google.com/archive/p/covalentdock/downloads

			76 systems (have't tested yet)

			From Schrondinger covalent datasets 38 systems

Xiaobo wan: /* Step 6 Run the minimization and MM/GBSA rescoreing */

2018-07-19T00:44:08Z

Step 6 Run the minimization and MM/GBSA rescoreing

← Older revision		Revision as of 00:44, 19 July 2018
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	==Step 6 Run the minimization and MM/GBSA rescoreing==		==Step 6 Run the minimization and MM/GBSA rescoreing==

	cd 6-Run-the-minimization-and-MMGBSA-rescoring		cd 6-Run-the-minimization-and-MMGBSA-rescoring
	~~First, check the protonation state of each linker after when using the chimera to add hydrogen~~
	~~second, the different H position of linkers will result in the different labelling number of the attached NH of lysine residue~~
	~~prepare the list for each linker containing two informations in XO44.charge.list file (default:xabs 1 1)~~

	bash ~~step7_fix_prolem_resubmit_MMPBSA.minimization~~.sh INDOCK.bump1000000000000.pose1000.20.5.5-~~xo4E-A-X44-X44-meta-xaaa~~-1-~~mini_end_GB~~		First, extract the each pose
	INDOCK.bump1000000000000.pose1000.20.5.5-~~xo4E-A-X44-X44-meta-xaaa~~-1-~~mini_end_GB~~ is the folder for runing minimization
			perl step1-split-poses.pl uniq.analysis.hqVA-M-ASF.dat.pdb


			the protonation state of each linker after when using the chimera to add hydrogen
			prepare the list for each linker containing charge information (default:0)

			bash qsub_run_automatic_pipeline_for_amber_minimization.sh INDOCK.bump1000000000000.pose1000.20.5.5-C000032628502-1-5 0
			INDOCK.bump1000000000000.pose1000.20.5.5-C000032628502-1-5 is the folder for runing minimization

	after minimization, then run the AMBER MMGBSA rescoring		after minimization, then run the AMBER MMGBSA rescoring

Xiaobo wan: /* Step 5 Analysis and combine the top1 pose from different structures */

2018-07-19T00:13:06Z

Step 5 Analysis and combine the top1 pose from different structures

← Older revision		Revision as of 00:13, 19 July 2018
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	bash step2-1-combine-check-job.sh lib1		bash step2-1-combine-check-job.sh lib1
	~~Inputfile~~ :		Input file :
	1) the ligand library folder name (lib1)		1) the ligand library folder name (lib1)

	extract the docking poses (you can also use ~~the~~ your own scripts to process your data)		extract the docking poses (you can also use your own scripts to process your data)

	bash step2-3-rank-poses.sh lib1		bash step2-3-rank-poses.sh lib1

	Input file :		Input file :
	1) the ligand library folder name (lib1)		1) the ligand library folder name (lib1)


	==Step 6 Run the minimization and MM/GBSA rescoreing==		==Step 6 Run the minimization and MM/GBSA rescoreing==

Xiaobo wan at 00:12, 19 July 2018

2018-07-19T00:12:40Z

← Older revision		Revision as of 00:12, 19 July 2018
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	==Step 5 Analysis and combine the top1 pose from different structures==		==Step 5 Analysis and combine the top1 pose from different structures==

	cd 5-Analysis-and-combine-the-top1-poses-from-different-structures		cd 5-Analysis-and-combine-the-top1-poses-from-different-structures
	after the covalent docking, analyze the docking results		after the covalent docking, analyze the docking results

	bash ~~step1_extract_the_best_score~~.sh ~~structure-list~~ lib1 ~~lib1.list~~		bash step2-1-combine-check-job.sh lib1
	Inputfile :		Inputfile :
	1~~) the list different structure folders (5K9A-B-X44,5K9A-C-X44)~~		1) the ligand library folder name (lib1)
	2) the ligand library folder name (lib1)
	~~3) the linker name list (lib1.list~~)

	~~combine~~ the docking ~~results~~		extract the docking poses (you can also use the your own scripts to process your data)

	bash ~~step3_combine~~-~~best~~-~~energy~~.sh ~~structure-list~~ lib1		bash step2-3-rank-poses.sh lib1

	Input file :		Input file :
	1~~) the list different structure folders (5K9A-B-X44,5K9A-C-X44)~~		1) the ligand library folder name (lib1)
	2) the ligand library folder name (lib1)
	~~Output file:~~
	~~1)sort.final.combine-new.aura-A-X63.list.dat rank all of the top1 pose for each linker~~
	~~2)submit.new.aura-A-X63.list.dat the name of structure file and linker~~

	==Step 6 Run the minimization and MM/GBSA rescoreing==		==Step 6 Run the minimization and MM/GBSA rescoreing==

Xiaobo wan: /* Step 4 run the covalent docking in gimel */

2018-07-19T00:03:43Z

Step 4 run the covalent docking in gimel

← Older revision		Revision as of 00:03, 19 July 2018
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	Define in the file qsub_fix-pipeline-for-dock-and-filter.sh		Define in the file qsub_fix-pipeline-for-dock-and-filter.sh

	scriptsdir=		scriptsdir=
	ligdir=
			ligdir=

	Input file :		Input file :

Xiaobo wan: /* Step 4 run the covalent docking in gimel */

2018-07-19T00:03:26Z

Step 4 run the covalent docking in gimel

← Older revision		Revision as of 00:03, 19 July 2018
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	2)the gate residue file (define the covalent modified cys in this file )		2)the gate residue file (define the covalent modified cys in this file )

	Define in the file		Define in the file qsub_fix-pipeline-for-dock-and-filter.sh
	~~scriptsdir=~~qsub_fix-pipeline-for-dock-and-filter.sh
			scriptsdir=
	ligdir=		ligdir=

Xiaobo wan: /* Step 4 run the covalent docking in gimel */

2018-07-19T00:02:19Z

Step 4 run the covalent docking in gimel

← Older revision		Revision as of 00:02, 19 July 2018
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	cd 4-run-the-covalent-docking		cd 4-run-the-covalent-docking

	contain a pharmacophore filter ( exclusion criteria that ligands should form hydrogen bonds with the ~~kinase hinge region~~, and the ~~shared pyrimidine 3-aminopyrazole scaffold~~ should ~~be within 2 Å compared to the crystal conformation~~)		contain a pharmacophore filter (exclusion criteria that ligands should form hydrogen bonds with the protein, and the ligand should form one hydrogen bond with protein)

	Prepare		Prepare
	1)the modified INDOCK file INDOCK.bump1000000000000.pose1000.20.5.5		1)the modified INDOCK file INDOCK.bump1000000000000.pose1000.20.5.5
	2)the gate residue file (define the ~~two residue~~ in the ~~SRC kinase domain MET341 VAL399)~~		2)the gate residue file (define the covalent modified cys in this file )

			Define in the file
			scriptsdir=qsub_fix-pipeline-for-dock-and-filter.sh
			ligdir=

	Input file :		Input file :
	1) the list different structure folders (~~5K9A~~-B-~~X44,5K9A-C-X44~~)		1) the list different structure folders (4iqA-A-AR6)
	2) the ligand library folder name (lib1)		2) the ligand library folder name (lib1)
	~~3) the linker name list (lib1.list)~~		bash qsub_fix-pipeline-for-dock-and-filter.sh run.list lib1
	bash ~~/mnt/nfs/home/xiaobo/UCSF_scripts/2018~~-4-3-~~covlanet_lysine_cys_wiki~~-~~tutorial/4~~-run~~-the-covalent-docking/qsub_multipe_jobs structure-~~list lib1 ~~lib1.list~~

	==Step 5 Analysis and combine the top1 pose from different structures==		==Step 5 Analysis and combine the top1 pose from different structures==

Xiaobo wan at 23:51, 18 July 2018

2018-07-18T23:51:30Z

← Older revision		Revision as of 23:51, 18 July 2018
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	bump_rigid 1000000000000.0		bump_rigid 1000000000000.0
	number_save 100		number_save 100
	number_write 100		number_write 100
	molecules_maximum 100000		molecules_maximum 100000
	electrostatic_scale 1.0		electrostatic_scale 1.0
	vdw_scale 1.0		vdw_scale 1.0
	bond_len 1.77		bond_len 1.77
	bond_ang1 124.18		bond_ang1 124.18
	bond_ang2 120.84		bond_ang2 120.84
	len_range 0.0		len_range 0.0
	len_step 0.1		len_step 0.1
	ang1_range 20.0		ang1_range 20.0
	ang2_range 20.0		ang2_range 20.0
	ang1_step 5		ang1_step 5
	ang2_step 5		ang2_step 5
	check_clashes no		check_clashes no
	per_atom_scores yes		per_atom_scores yes

Xiaobo wan at 23:49, 18 July 2018

2018-07-18T23:49:52Z

← Older revision		Revision as of 23:49, 18 July 2018
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	change the default parameters for covalent docking		change the default parameters for covalent docking

	~~bump_maximum 100~~		bump_rigid 1000000000000.0
	bump_rigid ~~100~~		number_save 100
	number_save ~~1000~~		number_write 100
	number_write ~~1000~~		molecules_maximum 100000
	molecules_maximum 100000		electrostatic_scale 1.0
	bond_len 1.61		vdw_scale 1.0
	bond_ang1 ~~121~~.02		bond_len 1.77
	bond_ang2 ~~107~~.36		bond_ang1 124.18
	len_range 0.0		bond_ang2 120.84
	len_step 0.1		len_range 0.0
	ang1_range 20.0		len_step 0.1
	ang2_range 20.0		ang1_range 20.0
	ang1_step 5		ang2_range 20.0
	ang2_step 5		ang1_step 5
	check_clashes no		ang2_step 5
	per_atom_scores yes		check_clashes no
			per_atom_scores yes


	==Step 4 run the covalent docking in gimel==		==Step 4 run the covalent docking in gimel==