D-I-TASSER P42684-D3

D-I-TASSER results for P42684-D3

[Click result.zip to download all results on this page]

Input Sequence in FASTA format

>P42684 (265 residues)
VYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFL
KEAAVMKEIKHPNLVQLLGVCTLEPPFYIVTEYMPYEEVAEELGRAASSSSVVPYLPRLP
ILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQASSGSPALPRKQRDKSPS
SLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVA
SLQHADGFSFTPAQQEANLVPPKCY

Predicted Secondary Structure

Sequence	20 40 60 80 100 120 140 160 180 200 220 240 260 \| \| \| \| \| \| \| \| \| \| \| \| \| VYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTLEPPFYIVTEYMPYEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQASSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPAQQEANLVPPKCY
Prediction	CCCCCCCCCCCSCCHHHCSSSSSSCCCCCCSSSSSSSCCCCCSSSSSSSCCCCCCHHHHHHHHHHHHHCCCCCSCSSSSSSSCCCCSSSSSSCCCCCSHHHHHHHCCCCCCCCCHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCSSSSCCCCCSSCCCCCCCCHHHCSCCCCCCSSSSSCCCCCCSSSSSCCCCCCCCCCCCCHHHHHCCCCCCCCCCCCCCCCHHHHHHHCCCCCCCCCCCCCCCCCCC
Confidence	9777879955404745518868861357968999999499827999980799764999999999998689933305889992599269999827999079999752677653209999999999988889999863021055673312355423112100365067632020235777333213567413553126775416775276246611263035452142126779999999402333311215855677777887779
	H:Helix; S:Strand; C:Coil

Predicted Solvent Accessibility

Sequence	20 40 60 80 100 120 140 160 180 200 220 240 260 \| \| \| \| \| \| \| \| \| \| \| \| \| VYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTLEPPFYIVTEYMPYEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQASSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPAQQEANLVPPKCY
Prediction	4142423456110437404034304441233001020575714000010366254363025005104605051002000000465100000000443302510354466443141033023024303100210312311144430243120200200222333364243032332213021113445300001024233334035446240203212513315713344352456543242043143242326354554445517
	Values range from 0 (buried residue) to 8 (highly exposed residue)

Predicted Contact, Hydrogen and Distance Map Used in D-I-TASSER simulation

Contact Map

Distance Map

Hydrogen bond networks

D-I-TASSER simulation is guided by the consensus contact map (left figure), distance map (middle figure) and Hydrogen bond network (right figure) derived based on confidence scores of AttentionPotential. In the contact, distance map and hydrogen bond networks, the axes mark the residue index along the sequence. For the contact map, each dot represents a residue pair with predicted contact, while for the distance map and hydrogen bond network, a color scale represents a distance of 1-20+ angstroms or a angle of 0-180 degree.

Top 10 threading templates used by D-I-TASSER

Rank

PDB
hit

ID1

ID2

Cov

Norm.
Zscore

Download
alignment

                  20                  40                  60                  80                 100                 120                 140                 160                 180                 200                 220                 240                 260

                   |                   |                   |                   |                   |                   |                   |                   |                   |                   |                   |                   |                   |

SS
Seq

CCCCCCCCCCCSCCHHHCSSSSSSCCCCCCSSSSSSSCCCCCSSSSSSSCCCCCCHHHHHHHHHHHHHCCCCCSCSSSSSSSCCCCSSSSSSCCCCCSHHHHHHHCCCCCCCCCHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCSSSSCCCCCSSCCCCCCCCHHHCSCCCCCCSSSSSCCCCCCSSSSSCCCCCCCCCCCCCHHHHHCCCCCCCCCCCCCCCCHHHHHHHCCCCCCCCCCCCCCCCCCC
VYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTLEPPFYIVTEYMPYEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQASSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPAQQEANLVPPKCY

6vg3A

0.18

0.17

5.38

1.68

SPARKS-K

---------KMHFPRSSLQPITTLGKSEFGEVFLAKAQGAETLVLVKSLQSKDQQQLDFRRELEMFGKLNHANVVRLLGLCREAEPHYMVLEYVDLGDLKQFLRISKSKDQPLSTKQKVALCTQVALGMEHLSNNRFVHKDLAVSAQRQVKVSALGLSKDVYNSEYYHFAWVPLRWMSPEAILEGDFSTHGEMPHGGQADDEVLAKARLPQPEGCPSKLYRLMQRCWALSPKDRPSFSEIASALGDS------------------

4cdsA

0.32

0.30

8.97

1.34

MUSTER

-------HDKWEIPRSEITLERKLGSGQFGEVYEGKWRNYNIEVAVKTLKEGTMSVEEFLQEAQIMKKLKHPNLVQLYGVCTKEPPIYIITEYMSHGSLLDYLRDCEGHTVNAQALLDMAAVASGMAYLESQFIHRDLAARNCLVGENNVKVADFGLARLIAK--------FPIKWTAPEAI-SYNRFSIKSDVWAFGLLWEIFTYGQVPYP---GMSGSEVIEQVERGYRMPRPQGCPEEELMLQCWNKSPEE--AETLHETMF

4cdsA1

0.43

0.25

7.42

1.81

FFAS-3D

-------HDKWEIPRSEITLERKLGSGQFGEVYEGKWRNYNIEVAVKTLKEGTMSVEEFLQEAQIMKKLKHPNLVQLYGVCTKEPPIYIITEYMSHGSLLDYLR--DCEGHTVNAQALLDMAAQVASGMAYLESQ-----------------------------------NFIHRDLAARNCLVGENNVVKVADFGLARL-----------------------------------------------------------------

1oplA

0.50

0.38

11.06

2.08

CNFpred

VYGVSPNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECN-----------RQEVNVVLLYMATQI-----SSAMEYLEKKNFI----------------------HRNLAARNCLVGVKVADFGLSRLM--GDTYTAHAGAKFPIKWTAPESLA-----NKFSIKSDVWAFGVLLWEIAT-----------------

2ac3A

0.14

0.10

3.46

0.83

DEthreader

--------SFSGRFEDVYQLQDVLGEGAHARVQTCINLITSQEYAVKIIEKQPHIRSRVFREVEMLYQCQHRNVLELIEFFEEEDRFYLVFEKMRGGSILSH-IH----FN-LEASVVVQDVAS-ALDFLHNKGIAHREVVEAFSEEAIYDKR-DLWSLGILYLLSG-YPPFVGR--------------------SDCGW-------------------------PDKDWAISCAAKDLIKLLVRDAKQR---------------

2x2kA

0.18

0.17

5.43

1.67

SPARKS-K

LSVDAFKIPKWEFPRKNLVLGKTLGEGEFGKVVKATAFHGYTTVAVKMLKENASELRDLLSEFNVLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVRA-LTMGDLISFAWQISQGMQYLAEMKLAARNILVAEGRKMKISDFGLSRVYEEDSVKSQGRIPVKWMAIESLFDH--IYTTQSDVTL-----------GGNPYPGIPPERLFNLLKTGHRMERPDNCSEEMYRLMLQCW-KQEPDKRPVFADISK

1irkA

0.18

0.17

5.65

0.50

MapAlign

--SSVFVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIETRVAVKTVNESARERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNP---GRPPPTLQEMIQMAAEIADGMAYLNAKKFVH-RDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSD----MWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLM

1irkA

0.21

0.20

6.49

0.39

CEthreader

--SSVFVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIETRVAVKTVNESARERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAPPPTLQEMIQMAAEIADGMAYLNAKKLAARNCMVAHDFTVKIGDFGMTRDIYYYRKGGKGLLPVRWMAPESLKDGVAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENK--

3genA

0.21

0.20

6.23

1.29

MUSTER

-------YGSWEIDPKDLTFLKELG---FGVVKYGKWRG-QYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKFLHRDLAARNCLVNDQGVKVSDFGLSRYVLDYTSSVGSKFPVRWSPPEVL-MYSKFSSKSDIWAFGLMWEIYSLGKMPYE---RFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADELDVMDEE--

4fl2A

0.23

0.19

5.92

0.86

HHsearch

EVYESPRPKEVYLDRKLLTLEKELGSGNFGTVKKGYYQMKVKTVAVKILKNEANLKDELLAEANVMQQLDNPYIVRMIGICE-AESWMLVMEMAELGPLNKYLQQN-R---H---------VKDKNIELVHQV-----SMGMKYLEESN----------------------FVHRDLAARNVLLVTQHSDFGLSKALRAENYYKAQTHGKWPVKWYA----PECINYYKFSSKSDVWSFGLMWEAFGKPYMKGKGERMGCPAGCP

(a)	ID1 is the number of template residues identical to query divided by number of aligned residues.
(b)	ID2 is the number of template residues identical to query divided by query sequence length.
(c)	Cov is equal the number of aligned template residues divided by query sequence length.
(d)	Norm. Zscore is the normalized Z-score of the threading alignments. A Normalized Z-score >1 means a good alignment and is highlighted in bold.
(e)	Download alignment lists the threading program used to identify the template, and provide the 3D structure of aligned regions of threading templates (threading[1-10].pdb.gz).
(f)	Template residues identical to query sequence are highlighted in color.

Top 1 final models from D-I-TASSER

Click to view	Rank^a	Download	Estimated TM-score^b
	1	model1.pdb.gz	0.6116

(a)

D-I-TASSER simulations generate a large ensemble of structural conformations, i.e. decoys. These decoys are clustered by SPICKER based on pairwise structure similarity to report up to five final models from the five largest clusters. Models are ranked in descending order of cluster size. If the simulations converge well, it is possible to have less than 5 models generated, which is usually an indication of good model quality.

(b)

The model confidence is quantitatified by estimated TM-score (eTM-score), calculated based on significance of threading template alignments, contact map satisfaction rate, mean absolute error between distance of model and distance of AttentionPotential, and convergence of D-I-TASSER simulations. eTM-score is typically in the range of [0, 1], with higher eTM-score signifies higher model confidence.

Proteins with similar structure

Top 10 structural analogs in PDB (as identified by TM-align)

Rank	PDB Hit	TM-score	RMSD^a	IDEN^a	Cov.	Download Alignment
1	7jy4A	0.70	3.63	0.209	0.872	model1_7jy4A.pdb.gz
2	3bkbA	0.70	3.70	0.187	0.857	model1_3bkbA.pdb.gz
3	2ogvA	0.70	3.88	0.173	0.883	model1_2ogvA.pdb.gz
4	4y93A	0.69	4.07	0.201	0.891	model1_4y93A.pdb.gz
5	1k9aB	0.69	3.72	0.193	0.864	model1_1k9aB.pdb.gz
6	5k5xA	0.69	3.92	0.174	0.883	model1_5k5xA.pdb.gz
7	2x2kA	0.69	3.86	0.147	0.864	model1_2x2kA.pdb.gz
8	1lufA	0.69	4.01	0.182	0.875	model1_1lufA.pdb.gz
9	5ek7A	0.69	4.02	0.176	0.883	model1_5ek7A.pdb.gz
10	4cdsA	0.69	3.46	0.293	0.838	model1_4cdsA.pdb.gz

(a)	Query structure is shown in cartoon, while the structural analog is displayed using backbone trace.
(b)	Ranking of proteins is based on TM-score of the structural alignment between the query structure and known structures in the PDB library.
(c)	RMSD^a is the RMSD between residues that are structurally aligned by TM-align.
(d)	IDEN^a is the percentage sequence identity in the structurally aligned region.
(e)	Cov. represents the coverage of the alignment by TM-align and is equal to the number of structurally aligned residues divided by length of the query protein.

Predicted Gene Ontology (GO) Terms

Molecular Function (MF)

GO term	Cscore^GO	Name
GO:0004672	0.99	protein kinase activity
GO:0005524	0.79	ATP binding
GO:0004713	0.77	protein tyrosine kinase activity
GO:0004715	0.75	non-membrane spanning protein tyrosine kinase activity
GO:0004674	0.73	protein serine/threonine kinase activity
GO:0019899	0.63	enzyme binding
GO:0008022	0.61	protein C-terminus binding
GO:0005080	0.61	protein kinase C binding
GO:0017124	0.60	SH3 domain binding
GO:0005102	0.56	receptor binding

Download full result of the above consensus prediction.

Click the graph to show a high resolution version.

(a)

Cscore^GO is the confidence score of predicted GO terms. Cscore^GO values range in between [0-1]; where a higher value indicates a better confidence in predicting the function using the template.

(b)

The graph shows the predicted terms within the Gene Ontology hierachy for Molecular Function. Confidently predicted terms are color coded by Cscore^GO:

[0.4,0.5)

[0.5,0.6)

[0.6,0.7)

[0.7,0.8)

[0.8,0.9)

[0.9,1.0]

Biological Process (BP)

GO term	Cscore^GO	Name
GO:0009987	0.95	cellular process
GO:0006468	0.92	protein phosphorylation
GO:0050794	0.87	regulation of cellular process
GO:0007165	0.82	signal transduction
GO:0018193	0.80	peptidyl-amino acid modification
GO:0046777	0.79	protein autophosphorylation
GO:0044699	0.76	single-organism process
GO:0018108	0.76	peptidyl-tyrosine phosphorylation
GO:0038083	0.75	peptidyl-tyrosine autophosphorylation
GO:0044763	0.74	single-organism cellular process
GO:0007166	0.73	cell surface receptor signaling pathway
GO:0048869	0.70	cellular developmental process
GO:0007169	0.69	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0002376	0.69	immune system process
GO:0050896	0.68	response to stimulus
GO:0048518	0.68	positive regulation of biological process
GO:0048583	0.67	regulation of response to stimulus
GO:0048522	0.67	positive regulation of cellular process
GO:0044767	0.67	single-organism developmental process
GO:0016043	0.66	cellular component organization
GO:0080090	0.65	regulation of primary metabolic process
GO:0060255	0.65	regulation of macromolecule metabolic process
GO:0048584	0.65	positive regulation of response to stimulus
GO:0031323	0.65	regulation of cellular metabolic process
GO:0009966	0.65	regulation of signal transduction
GO:0006950	0.65	response to stress
GO:1902531	0.64	regulation of intracellular signal transduction
GO:0048523	0.64	negative regulation of cellular process
GO:0031325	0.64	positive regulation of cellular metabolic process
GO:0010604	0.64	positive regulation of macromolecule metabolic process
GO:0009653	0.64	anatomical structure morphogenesis
GO:0001932	0.64	regulation of protein phosphorylation
GO:0050776	0.63	regulation of immune response
GO:0043410	0.63	positive regulation of MAPK cascade
GO:0007155	0.63	cell adhesion
GO:0098602	0.62	single organism cell adhesion
GO:0032989	0.62	cellular component morphogenesis
GO:0002768	0.62	immune response-regulating cell surface receptor signaling pathway
GO:0002757	0.62	immune response-activating signal transduction
GO:0070374	0.61	positive regulation of ERK1 and ERK2 cascade
GO:0038096	0.61	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0034446	0.61	substrate adhesion-dependent cell spreading
GO:0031324	0.61	negative regulation of cellular metabolic process
GO:0010605	0.61	negative regulation of macromolecule metabolic process
GO:0009968	0.61	negative regulation of signal transduction
GO:0007173	0.61	epidermal growth factor receptor signaling pathway
GO:0070373	0.60	negative regulation of ERK1 and ERK2 cascade
GO:0035556	0.59	intracellular signal transduction
GO:0042127	0.56	regulation of cell proliferation
GO:0030154	0.55	cell differentiation
GO:0065009	0.52	regulation of molecular function
GO:0051239	0.51	regulation of multicellular organismal process
GO:0050790	0.51	regulation of catalytic activity
GO:0048856	0.51	anatomical structure development
GO:0044093	0.51	positive regulation of molecular function
GO:0042221	0.51	response to chemical
GO:0065008	0.50	regulation of biological quality
GO:0051128	0.50	regulation of cellular component organization
GO:0050793	0.50	regulation of developmental process
GO:0043067	0.50	regulation of programmed cell death
GO:0033674	0.50	positive regulation of kinase activity
GO:0032879	0.50	regulation of localization

Download full result of the above consensus prediction.

Click the graph to show a high resolution version.

(a)

Cscore^GO is the confidence score of predicted GO terms. Cscore^GO values range in between [0-1]; where a higher value indicates a better confidence in predicting the function using the template.

(b)

The graph shows the predicted terms within the Gene Ontology hierachy for Biological Process. Confidently predicted terms are color coded by Cscore^GO:

[0.4,0.5)

[0.5,0.6)

[0.6,0.7)

[0.7,0.8)

[0.8,0.9)

[0.9,1.0]

Cellular Component (CC)

GO term	Cscore^GO	Name
GO:0044464	1.00	cell part
GO:0044424	0.87	intracellular part
GO:0016020	0.83	membrane
GO:0005886	0.76	plasma membrane
GO:0044425	0.69	membrane part
GO:0043226	0.65	organelle
GO:0044444	0.64	cytoplasmic part
GO:0005737	0.64	cytoplasm
GO:0044459	0.63	plasma membrane part
GO:0043229	0.60	intracellular organelle
GO:0043227	0.59	membrane-bounded organelle
GO:0043231	0.54	intracellular membrane-bounded organelle

Download full result of the above consensus prediction.

Click the graph to show a high resolution version.

(a)

Cscore^GO is the confidence score of predicted GO terms. Cscore^GO values range in between [0-1]; where a higher value indicates a better confidence in predicting the function using the template.

(b)

The graph shows the predicted terms within the Gene Ontology hierachy for Cellular Component. Confidently predicted terms are color coded by Cscore^GO:

[0.4,0.5)

[0.5,0.6)

[0.6,0.7)

[0.7,0.8)

[0.8,0.9)

[0.9,1.0]

Predicted Enzyme Commission (EC) Numbers

Top 5 enzyme homologs in PDB

Rank	Cscore^EC	PDB Hit	TM-score	RMSD^a	IDEN^a	Cov.	EC Number	Predicted Active Site Residues
1	0.223	3efwB	0.620	3.97	0.161	0.789	2.7.11.1	176
2	0.185	3cokB	0.601	4.29	0.134	0.789	2.7.11.21	25,32,45,77
3	0.093	1sm2A	0.640	3.92	0.181	0.807	2.7.10.2	NA
4	0.092	3fqeA	0.661	3.47	0.167	0.807	2.7.10.2	NA
5	0.087	3e62A	0.674	3.94	0.141	0.860	2.7.10.2	NA

	Click on the radio buttons to visualize predicted active site residues.
(a)	Cscore^EC is the confidence score for the Enzyme Commission (EC) number prediction. Cscore^EC values range in between [0-1]; where a higher score indicates a more reliable EC number prediction.
(b)	TM-score is a measure of global structural similarity between query and template protein.
(c)	RMSD^a is the RMSD between residues that are structurally aligned by TM-align.
(d)	IDEN^a is the percentage sequence identity in the structurally aligned region.
(e)	Cov. represents the coverage of global structural alignment and is equal to the number of structurally aligned residues divided by length of the query protein.

Predicted Ligand Binding Sites

Template proteins with similar binding site:

Rank	Cscore^LB	PDB Hit	TM-score	RMSD^a	IDEN^a	Cov.	BS-score	Lig. Name	Download Complex	Predicted binding site residues
1	0.54	3lcsA	0.706	3.90	0.198	0.891	1.04	STU	complex1.pdb.gz	24,26,27,32,45,47,91,92,93,94,97,98
2	0.27	2pwlB	0.689	3.78	0.176	0.864	1.02	ABG	complex2.pdb.gz	24,25,27,32,45,47,91,92,154
3	0.27	3aoxA	0.677	3.82	0.196	0.853	0.86	EMH	complex3.pdb.gz	22,24,45,47,75,91,92,93,94
4	0.25	2fgiB	0.654	3.96	0.169	0.845	1.04	PD1	complex4.pdb.gz	24,25,26,32,45,47,62,75,89,91,92,93,94,95,96,101
5	0.24	3gqlC	0.642	4.12	0.178	0.842	0.85	GQL	complex5.pdb.gz	24,25,46,48,62,75,92,93,94
6	0.07	1t46A	0.702	3.88	0.175	0.887	0.96	STI	complex6.pdb.gz	24,32,45,46,47,62,65,66,89,91,93,94,97,139,140,153,154
7	0.04	3cd3A	0.684	3.72	0.180	0.845	1.15	STU	complex7.pdb.gz	11,41,43,76,77,78

	Click on the radio buttons to visualize predicted binding site and residues.
(a)	Cscore^LB is the confidence score of predicted binding site. Cscore^LB values range in between [0-1]; where a higher score indicates a more reliable ligand-binding site prediction.
(b)	BS-score is a measure of local similarity (sequence & structure) between template binding site and predicted binding site in the query structure. Based on large scale benchmarking analysis, we have observed that a BS-score >1 reflects a significant local match between the predicted and template binding site.
(c)	TM-score is a measure of global structural similarity between query and template protein.
(d)	RMSD^a the RMSD between residues that are structurally aligned by TM-align.
(e)	IDEN^a is the percentage sequence identity in the structurally aligned region.
(f)	Cov. represents the coverage of global structural alignment and is equal to the number of structurally aligned residues divided by length of the query protein.

[Click result.zip to download all results on this page]

References:
1.	Wei Zheng, Chengxin Zhang, Yang Li, Robin Pearce, Eric W. Bell, Yang Zhang. Folding non-homology proteins by coupling deep-learning contact maps with I-TASSER assembly simulations. In preparation, 2020.