SWISS-MODEL Homology Modelling Report

Model Building Report

This document lists the results for the homology modelling project "6B1U-P54646" submitted to SWISS-MODEL workspace on April 7, 2022, 8:07 p.m..The submitted primary amino acid sequence is given in Table T1.

If you use any results in your research, please cite the relevant publications:

• Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F.T., de Beer, T.A.P., Rempfer, C., Bordoli, L., Lepore, R., Schwede, T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46(W1), W296-W303 (2018).
• Bienert, S., Waterhouse, A., de Beer, T.A.P., Tauriello, G., Studer, G., Bordoli, L., Schwede, T. The SWISS-MODEL Repository - new features and functionality. Nucleic Acids Res. 45, D313-D319 (2017).
• Studer, G., Tauriello, G., Bienert, S., Biasini, M., Johner, N., Schwede, T. ProMod3 - A versatile homology modelling toolbox. PLOS Comp. Biol. 17(1), e1008667 (2021).
• Studer, G., Rempfer, C., Waterhouse, A.M., Gumienny, G., Haas, J., Schwede, T. QMEANDisCo - distance constraints applied on model quality estimation. Bioinformatics 36, 1765-1771 (2020).
• Bertoni, M., Kiefer, F., Biasini, M., Bordoli, L., Schwede, T. Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Scientific Reports 7 (2017).

Results

The user uploaded a template structure to use for the modelling process.

Models

The following model was built (see Materials and Methods "Model Building"):

Model #01	File	Built with	Oligo-State	Ligands	GMQE	QMEANDisCo Global
	PDB	ProMod3 3.2.1	hetero-1-1-1-mer	2 x AMP: AMP; 1 x CG7: CG7; 1 x STU: STU;	0.78	0.74 ± 0.05

Included Ligands

Target                   MGNTSSERAALERHGGHKTPRRDSSGGTKDGDRPKILMDSPEDADLFHSEEIKAP
template_upload.1.B      -------------------------------------------------------

Target                   EKEEFLAWQHDLEVNDKAPAQARPTVFRWTGGGKEVYLSGSFNNWSKLPLTRSHN
template_upload.1.B      ----------------------RPTVFRWTGGGKEVYLSGSFNNWSKLPLTRSHN

Target                   NFVAILDLPEGEHQYKFFVDGQWTHDPSEPIVTSQLGTVNNIIQVKKTDFEVFDA
template_upload.1.B      NFVAILDLPEGEHQYKFFVDGQWTHDPSEPIVTSQLGTVNNIIQVKKTDFEVFDA

Target                   LMVDSQKCSDVSELSSSPPGPYHQEPYVCKPEERFRAPPILPPHLLQVILNKDTG
template_upload.1.B      LMVDSQKCSD---------GPYHQEPYVCKPEERFRAPPILPPHLLQVILNKDTG

Target                   ISCDPALLPEPNHVMLNHLYALSIKDGVMVLSATHRYKKKYVTTLLYKPI
template_upload.1.B      ISCDPALLPEPNHVMLNHLYALSIKDGVMVLSATHRYKKKYVTTLLYKPI

Target                   AEKQKHDGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLD
template_upload.1.A      ------DGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLD

Target                   VVGKIKREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRV
template_upload.1.A      VVGKIKREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRV

Target                   EEMEARRLFQQILSAVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSD
template_upload.1.A      EEMEARRLFQQILSAVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSD

Target                   GEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDEHVPT
template_upload.1.A      GEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDEHVPT

Target                   LFKKIRGGVFYIPEYLNRSVATLLMHMLQVDPLKRATIKDIREHEWFKQDLPSYL
template_upload.1.A      LFKKIRGGVFYIPEYLNRSVATLLMHMLQVDPLKRATIKDIREHEWFKQGLPSYL

Target                   FPEDPSYDANVIDDEAVKEVCEKFECTESEVMNSLYSGDPQDQLAVAYHLIIDNR
template_upload.1.A      FPEDPSYDANVIDDEAVKEVCEKF---ESEVMNSLY----QDQLAVAYHLIIDNR

Target                   RIMNQASEFYLASSPPSGSFMDDSAMHIPPGLKPHPERMPPLIADSPKARCPLDA
template_upload.1.A      RIMNQASEFYLASSP----------------LKPHPERMPPLI------------

Target                   LNTTKPKSLAVKKAKWHLGIRSQSKPYDIMAEVYRAMKQLDFEWKVVNAYHLRVR
template_upload.1.A      -----------KKAKWHLGIRSQSKPYDIMAEVYRAMKQLDFEWKVVNAYHLRVR

Target                   RKNPVTGNYVKMSLQLYLVDNRSYLLDFKSIDDEVVEQRSGSSTPQRSCSAAGLH
template_upload.1.A      RKNPVTGNYVKMSLQLYLVDNRSYLLDFKSIDDP----RLGSHT-----------

Target                   RPRSSFDSTTAESHSLSGSLTGSLTGSTLSSVSPRLGSHTMDFFEMCASLITTLA
template_upload.1.A      ----------------------------------------MDFFEMCASLITTL-

Target                   R
template_upload.1.A      -

Target                   ETVISSDSSPAVENEHPQETPESNNSVYTSFMKSHRCYDLIPTSSKLVVFDTSLQ
template_upload.1.C      ------------------------NSVYTSFMKSHRCYDLIPTSSKLVVFDTSLQ

Target                   VKKAFFALVTNGVRAAPLWDSKKQSFVGMLTITDFINILHRYYKSALVQIYELEE
template_upload.1.C      VKKAFFALVTNGVRAAPLWDSKKQSFVGMLTITDFINILHRYYKSALVQIYELEE

Target                   HKIETWREVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYI
template_upload.1.C      HKIETWREVYLQ-SFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYI

Target                   LTHKRILKFLKLFITEFPKPEFMSKSLEELQIGTYANIAMVRTTTPVYVALGIFV
template_upload.1.C      LTHKRILKFLKLFITEFPKPEFMSKSLEELQIGTYANIAMVRTTTPVYVALGIFV

Target                   QHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRSHYFEGV
template_upload.1.C      QHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRSHYFEGV

Target                   LKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALVLTGGEKKP
template_upload.1.C      LKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALVLT------

Materials and Methods

Template Selection

For each identified template, the template's quality has been predicted from features of the target-template alignment. The templates with the highest quality have then been selected for model building.

User Template Alignment

Model Building

Models are built based on the target-template alignment using ProMod3 (Studer et al.). Coordinates which are conserved between the target and the template are copied from the template to the model. Insertions and deletions are remodelled using a fragment library. Side chains are then rebuilt. Finally, the geometry of the resulting model is regularized by using a force field.

Model Quality Estimation

The global and per-residue model quality has been assessed using the QMEAN scoring function (Studer et al.).

Ligand Modelling

Ligands present in the template structure are transferred by homology to the model when the following criteria are met: (a) The ligands are annotated as biologically relevant in the template library, (b) the ligand is in contact with the model, (c) the ligand is not clashing with the protein, (d) the residues in contact with the ligand are conserved between the target and the template. If any of these four criteria is not satisfied, a certain ligand will not be included in the model. The model summary includes information on why and which ligand has not been included.

Oligomeric State Conservation

The quaternary structure annotation of the template is used to model the target sequence in its oligomeric form. The method (Bertoni et al.) is based on a supervised machine learning algorithm, Support Vector Machines (SVM), which combines interface conservation, structural clustering, and other template features to provide a quaternary structure quality estimate (QSQE). The QSQE score is a number between 0 and 1, reflecting the expected accuracy of the interchain contacts for a model built based a given alignment and template. Higher numbers indicate higher reliability. This complements the GMQE score which estimates the accuracy of the tertiary structure of the resulting model.

References

• BLAST
  Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., Madden, T.L. BLAST+: architecture and applications. BMC Bioinformatics 10, 421-430 (2009).
• HHblits
  Steinegger, M., Meier, M., Mirdita, M., Vöhringer, H., Haunsberger, S. J., Söding, J. HH-suite3 for fast remote homology detection and deep protein annotation. BMC Bioinformatics 20, 473 (2019).

Table T1:

Primary amino acid sequences for which templates were searched and models were built.

Table T2: