Protein assemblies are involved in many important biological processes. Solid-state NMR (SSNMR) spectroscopy is a technique suitable for the structural characterization of samples with high molecular weight and thus can be applied to such assemblies. A significant bottleneck in terms of both effort and time required is the manual identification of unambiguous intermolecular contacts. This is particularly challenging for homo-oligomeric complexes, where simple uniform labeling may not be effective. We tackled this challenge by exploiting coevolution analysis to extract information on homo-oligomeric interfaces from NMR-derived ambiguous contacts. After removing the evolutionary couplings (ECs) that are already satisfied by the 3D structure of the monomer, the predicted ECs are matched with the automatically generated list of experimental contacts. This approach provides a selection of potential interface residues that is used directly in monomer–monomer docking calculations. We validated the protocol on tetrameric L-asparaginase II and dimeric Sod1.

A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts / Sala D.; Cerofolini L.; Fragai M.; Giachetti A.; Luchinat C.; Rosato A.. - In: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL. - ISSN 2001-0370. - ELETTRONICO. - 18:(2020), pp. 114-124. [10.1016/j.csbj.2019.12.002]

A protocol to automatically calculate homo-oligomeric protein structures through the integration of evolutionary constraints and NMR ambiguous contacts

Sala D.
Methodology
;
Cerofolini L.
Methodology
;
Fragai M.
Conceptualization
;
Giachetti A.
Membro del Collaboration Group
;
Luchinat C.
Membro del Collaboration Group
;
Rosato A.
Supervision
2020

Abstract

Protein assemblies are involved in many important biological processes. Solid-state NMR (SSNMR) spectroscopy is a technique suitable for the structural characterization of samples with high molecular weight and thus can be applied to such assemblies. A significant bottleneck in terms of both effort and time required is the manual identification of unambiguous intermolecular contacts. This is particularly challenging for homo-oligomeric complexes, where simple uniform labeling may not be effective. We tackled this challenge by exploiting coevolution analysis to extract information on homo-oligomeric interfaces from NMR-derived ambiguous contacts. After removing the evolutionary couplings (ECs) that are already satisfied by the 3D structure of the monomer, the predicted ECs are matched with the automatically generated list of experimental contacts. This approach provides a selection of potential interface residues that is used directly in monomer–monomer docking calculations. We validated the protocol on tetrameric L-asparaginase II and dimeric Sod1.
2020
18
114
124
Sala D.; Cerofolini L.; Fragai M.; Giachetti A.; Luchinat C.; Rosato A.
File in questo prodotto:
File Dimensione Formato  
CSBJ_evolutionarycontraints_2020.pdf

accesso aperto

Descrizione: Published version
Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 2.37 MB
Formato Adobe PDF
2.37 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1190062
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact