Improving folding properties of computationally designed proteins

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Standard

Improving folding properties of computationally designed proteins. / Bjerre, Benjamin; Nissen, Jakob; Madsen, Mikkel; Kamarauskaite, Jurate; Norrild, Rasmus K; Holm, Peter C; Nordentoft, Mathilde K; O'Shea, Charlotte; Willemoës, Martin; Johansson, Kristoffer E; Winther, Jakob R.

I: Protein Engineering Design and Selection (Print), Bind 32, Nr. 3, 13.12.2019, s. 145-151.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Bjerre, B, Nissen, J, Madsen, M, Kamarauskaite, J, Norrild, RK, Holm, PC, Nordentoft, MK, O'Shea, C, Willemoës, M, Johansson, KE & Winther, JR 2019, 'Improving folding properties of computationally designed proteins', Protein Engineering Design and Selection (Print), bind 32, nr. 3, s. 145-151. https://doi.org/10.1093/protein/gzz025

APA

Bjerre, B., Nissen, J., Madsen, M., Kamarauskaite, J., Norrild, R. K., Holm, P. C., Nordentoft, M. K., O'Shea, C., Willemoës, M., Johansson, K. E., & Winther, J. R. (2019). Improving folding properties of computationally designed proteins. Protein Engineering Design and Selection (Print), 32(3), 145-151. https://doi.org/10.1093/protein/gzz025

Vancouver

Bjerre B, Nissen J, Madsen M, Kamarauskaite J, Norrild RK, Holm PC o.a. Improving folding properties of computationally designed proteins. Protein Engineering Design and Selection (Print). 2019 dec. 13;32(3):145-151. https://doi.org/10.1093/protein/gzz025

Author

Bjerre, Benjamin ; Nissen, Jakob ; Madsen, Mikkel ; Kamarauskaite, Jurate ; Norrild, Rasmus K ; Holm, Peter C ; Nordentoft, Mathilde K ; O'Shea, Charlotte ; Willemoës, Martin ; Johansson, Kristoffer E ; Winther, Jakob R. / Improving folding properties of computationally designed proteins. I: Protein Engineering Design and Selection (Print). 2019 ; Bind 32, Nr. 3. s. 145-151.

Bibtex

@article{0001c1d4f38c484c88f2081163576799,

title = "Improving folding properties of computationally designed proteins",

abstract = "While the field of computational protein design has witnessed amazing progression in recent years, folding properties still constitute a significant barrier towards designing new and larger proteins. In order to assess and improve folding properties of designed proteins, we have developed a genetics-based folding assay and selection system based on the essential enzyme, orotate phosphoribosyl transferase from Escherichia coli. This system allows for both screening of candidate designs with good folding properties and genetic selection of improved designs. Thus, we identified single amino acid substitutions in two failed designs that rescued poorly folding and unstable proteins. Furthermore, when these substitutions were transferred into a well-structured design featuring a complex folding profile, the resulting protein exhibited native-like cooperative folding with significantly improved stability. In protein design, a single amino acid can make the difference between folding and misfolding, and this approach provides a useful new platform to identify and improve candidate designs.",

author = "Benjamin Bjerre and Jakob Nissen and Mikkel Madsen and Jurate Kamarauskaite and Norrild, {Rasmus K} and Holm, {Peter C} and Nordentoft, {Mathilde K} and Charlotte O'Shea and Martin Willemo{\"e}s and Johansson, {Kristoffer E} and Winther, {Jakob R}",

year = "2019",

month = dec,

day = "13",

doi = "10.1093/protein/gzz025",

language = "English",

volume = "32",

pages = "145--151",

journal = "Protein Engineering, Design and Selection",

issn = "1741-0126",

publisher = "Oxford University Press",

number = "3",

}

RIS

TY - JOUR

T1 - Improving folding properties of computationally designed proteins

AU - Bjerre, Benjamin

AU - Nissen, Jakob

AU - Madsen, Mikkel

AU - Kamarauskaite, Jurate

AU - Norrild, Rasmus K

AU - Holm, Peter C

AU - Nordentoft, Mathilde K

AU - O'Shea, Charlotte

AU - Willemoës, Martin

AU - Johansson, Kristoffer E

AU - Winther, Jakob R

PY - 2019/12/13

Y1 - 2019/12/13

N2 - While the field of computational protein design has witnessed amazing progression in recent years, folding properties still constitute a significant barrier towards designing new and larger proteins. In order to assess and improve folding properties of designed proteins, we have developed a genetics-based folding assay and selection system based on the essential enzyme, orotate phosphoribosyl transferase from Escherichia coli. This system allows for both screening of candidate designs with good folding properties and genetic selection of improved designs. Thus, we identified single amino acid substitutions in two failed designs that rescued poorly folding and unstable proteins. Furthermore, when these substitutions were transferred into a well-structured design featuring a complex folding profile, the resulting protein exhibited native-like cooperative folding with significantly improved stability. In protein design, a single amino acid can make the difference between folding and misfolding, and this approach provides a useful new platform to identify and improve candidate designs.

AB - While the field of computational protein design has witnessed amazing progression in recent years, folding properties still constitute a significant barrier towards designing new and larger proteins. In order to assess and improve folding properties of designed proteins, we have developed a genetics-based folding assay and selection system based on the essential enzyme, orotate phosphoribosyl transferase from Escherichia coli. This system allows for both screening of candidate designs with good folding properties and genetic selection of improved designs. Thus, we identified single amino acid substitutions in two failed designs that rescued poorly folding and unstable proteins. Furthermore, when these substitutions were transferred into a well-structured design featuring a complex folding profile, the resulting protein exhibited native-like cooperative folding with significantly improved stability. In protein design, a single amino acid can make the difference between folding and misfolding, and this approach provides a useful new platform to identify and improve candidate designs.

U2 - 10.1093/protein/gzz025

DO - 10.1093/protein/gzz025

M3 - Journal article

C2 - 31553452

VL - 32

SP - 145

EP - 151

JO - Protein Engineering, Design and Selection

JF - Protein Engineering, Design and Selection

SN - 1741-0126

IS - 3

ER -

ID: 232910751

Biologisk Institut