Modeling membrane proteins: The importance of cysteine amino-acids

Evgeni Grazhdankin, Michal Stepniewski, Henri Xhaard

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Computational modeling of membrane proteins is critical to understand biochemical systems and to support chemical biology. In this work, we use a dataset of 448 non-redundant membrane protein chains to expose a "rule" that governs membrane protein structure: free cysteine thiols are not found accessible to oxidative compartments such as the extracellular space, but are rather involved in disulphide bridges. Taking as examples the 1018 three-dimensional models produced during the GPCR Dock 2008, 2010 and 2013 competitions and 390 models for a GPCR target in CASP13, we show that this rule was not accounted for by the modeling community. We thus highlight a new direction for model development that should lead to more accurate membrane protein models, especially in the loop domains.

Originalspråkengelska
Artikelnummer107400
TidskriftJournal of Structural Biology
Volym209
Utgåva1
Antal sidor9
ISSN1047-8477
DOI
StatusPublicerad - 1 jan 2020
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi
  • 317 Farmaci

Citera det här

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Modeling membrane proteins : The importance of cysteine amino-acids. / Grazhdankin, Evgeni; Stepniewski, Michal ; Xhaard, Henri.

I: Journal of Structural Biology, Vol. 209, Nr. 1, 107400, 01.01.2020.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Modeling membrane proteins

T2 - The importance of cysteine amino-acids

AU - Grazhdankin, Evgeni

AU - Stepniewski, Michal

AU - Xhaard, Henri

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Computational modeling of membrane proteins is critical to understand biochemical systems and to support chemical biology. In this work, we use a dataset of 448 non-redundant membrane protein chains to expose a "rule" that governs membrane protein structure: free cysteine thiols are not found accessible to oxidative compartments such as the extracellular space, but are rather involved in disulphide bridges. Taking as examples the 1018 three-dimensional models produced during the GPCR Dock 2008, 2010 and 2013 competitions and 390 models for a GPCR target in CASP13, we show that this rule was not accounted for by the modeling community. We thus highlight a new direction for model development that should lead to more accurate membrane protein models, especially in the loop domains.

AB - Computational modeling of membrane proteins is critical to understand biochemical systems and to support chemical biology. In this work, we use a dataset of 448 non-redundant membrane protein chains to expose a "rule" that governs membrane protein structure: free cysteine thiols are not found accessible to oxidative compartments such as the extracellular space, but are rather involved in disulphide bridges. Taking as examples the 1018 three-dimensional models produced during the GPCR Dock 2008, 2010 and 2013 competitions and 390 models for a GPCR target in CASP13, we show that this rule was not accounted for by the modeling community. We thus highlight a new direction for model development that should lead to more accurate membrane protein models, especially in the loop domains.

KW - CASP

KW - Cysteine

KW - DOCKING

KW - Disulphide bridges

KW - GPCR

KW - GPCR dock

KW - LIGANDS

KW - Loop modeling

KW - Membrane proteins

KW - Molecular modeling

KW - STRUCTURE PREDICTION

KW - SYMMETRY

KW - TOPOLOGY

KW - 1182 Biochemistry, cell and molecular biology

KW - 317 Pharmacy

U2 - 10.1016/j.jsb.2019.10.002

DO - 10.1016/j.jsb.2019.10.002

M3 - Article

VL - 209

JO - Journal of Structural Biology

JF - Journal of Structural Biology

SN - 1047-8477

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