D-I-TASSER P08473

D-I-TASSER results for P08473

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

Summary of the Protein

Uniprot ID: P08473
Protein Name: Neprilysin
Gene Name: MME

Input Sequence in FASTA format

>P08473 (750 residues)
MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSS
DCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKD
VLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGA
SWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKE
ACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLY
NKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILT
KYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNME
NAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERI
GYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAA
VVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKD
GDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYR
AYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRII
GTLQNSAEFSEAFHCRKNSYMNPEKKCRVW

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

Contact Map

Distance Map

D-I-TASSER simulation is guided by the consensus contact map (left figure) and distance map (right figure) derived based on confidence scores of DeepPotential. 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.

Information of Domain

No. of Domain	Domain	Domain Boundary	Length of Domain	Models of Domain	Sequence
1	P08473-D1	1-750	750		MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYNKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW

Top 1 final models from D-I-TASSER

Click to view	Rank^a	Download	Estimated TM-score^b
	1	model1.pdb.gz	0.961

(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 DeepPotential, 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	1r1hA	0.93	0.28	1.000	0.928	model1_1r1hA.pdb.gz
2	3dwbA	0.85	1.66	0.403	0.880	model1_3dwbA.pdb.gz
3	3zukA	0.82	2.15	0.302	0.861	model1_3zukA.pdb.gz
4	4iuwA	0.78	2.62	0.223	0.832	model1_4iuwA.pdb.gz
5	6rowA	0.75	2.21	0.255	0.788	model1_6rowA.pdb.gz
6	4z24A	0.23	8.82	0.032	0.395	model1_4z24A.pdb.gz
7	3iygQ	0.19	8.21	0.046	0.308	model1_3iygQ.pdb.gz
8	3akfA1	0.16	6.85	0.021	0.235	model1_3akfA1.pdb.gz
9	2f2fB	0.16	5.85	0.063	0.208	model1_2f2fB.pdb.gz
10	3dkqA	0.14	6.47	0.023	0.197	model1_3dkqA.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:0008233	0.99	peptidase activity
GO:0070011	0.98	peptidase activity, acting on L-amino acid peptides
GO:0008237	0.96	metallopeptidase activity
GO:0004175	0.87	endopeptidase activity
GO:0004222	0.83	metalloendopeptidase activity
GO:0043167	0.68	ion binding
GO:0046872	0.67	metal ion binding
GO:0008270	0.65	zinc ion binding
GO:0042277	0.61	peptide 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:0071704	0.89	organic substance metabolic process
GO:0044699	0.89	single-organism process
GO:0044238	0.89	primary metabolic process
GO:0009987	0.89	cellular process
GO:0043170	0.88	macromolecule metabolic process
GO:0006508	0.87	proteolysis
GO:0044237	0.80	cellular metabolic process
GO:0032502	0.80	developmental process
GO:0044763	0.79	single-organism cellular process
GO:0048856	0.78	anatomical structure development
GO:0044767	0.78	single-organism developmental process
GO:0006807	0.77	nitrogen compound metabolic process
GO:0034641	0.76	cellular nitrogen compound metabolic process
GO:0006518	0.75	peptide metabolic process
GO:0048869	0.72	cellular developmental process
GO:0048513	0.69	animal organ development
GO:0032501	0.69	multicellular organismal process
GO:0003008	0.66	system process
GO:0050896	0.62	response to stimulus
GO:0044710	0.60	single-organism metabolic process
GO:1901360	0.59	organic cyclic compound metabolic process
GO:0046483	0.59	heterocycle metabolic process
GO:0044281	0.59	small molecule metabolic process
GO:0042221	0.59	response to chemical
GO:0010033	0.58	response to organic substance
GO:0009628	0.58	response to abiotic stimulus
GO:0051716	0.57	cellular response to stimulus
GO:0050877	0.57	neurological system process
GO:0090399	0.56	replicative senescence
GO:0071493	0.56	cellular response to UV-B
GO:0071492	0.56	cellular response to UV-A
GO:0071345	0.56	cellular response to cytokine stimulus
GO:0065007	0.56	biological regulation
GO:0050435	0.56	beta-amyloid metabolic process
GO:0046449	0.56	creatinine metabolic process
GO:0019233	0.56	sensory perception of pain
GO:0001822	0.56	kidney development

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	0.95	cell part
GO:0044424	0.87	intracellular part
GO:0016020	0.86	membrane
GO:0044444	0.82	cytoplasmic part
GO:0043226	0.74	organelle
GO:0043227	0.73	membrane-bounded organelle
GO:0043229	0.72	intracellular organelle
GO:0043231	0.71	intracellular membrane-bounded organelle
GO:0005886	0.70	plasma membrane
GO:0031988	0.63	membrane-bounded vesicle
GO:0099503	0.61	secretory vesicle
GO:0045202	0.57	synapse
GO:0044306	0.57	neuron projection terminus
GO:0030425	0.57	dendrite
GO:0030424	0.57	axon
GO:0008021	0.57	synaptic vesicle
GO:0005903	0.57	brush border
GO:0005737	0.57	cytoplasm

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	0.215	3dwbA	0.855	1.66	0.403	0.880	3.4.24.71	NA
2	0.060	1ti6A	0.319	8.08	0.038	0.497	1.97.1.2	NA
3	0.060	2bklB	0.291	7.49	0.038	0.432	3.4.21.26	NA
4	0.060	2cvpA	0.292	7.34	0.052	0.429	5.3.1.9	NA
5	0.060	1t3tA	0.296	8.76	0.030	0.493	6.3.5.3	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:

Click to view	Rank	Cscore^LB	PDB Hit	TM-score	RMSD^a	IDEN^a	Cov.	BS-score	Lig. Name	Download Complex	Predicted binding site residues
	1	0.86	1y8jA	0.927	0.31	1.000	0.928	1.51	STS	complex1.pdb.gz	103,107,111,543,544,564,580,581,584,585,588,647,694,712,718

	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, Qiqige Wuyun, Yang Li, Quancheng Liu, Xiaogen Zhou, Yiheng Zhu, P. Lydia Freddolino, Yang Zhang. Integrating deep learning potentials with I-TASSER for single- and multi-domain protein structure prediction. Submitted. 2023.