Protein Engineering, Design and Selection, Volume (30), No (9), Year (2017-12) , Pages (593-601)

Title : ( Insights from engineering the Affibody-Fc interaction with a computational-experimental method )

Authors: MASOUMEH NOSRATI , Sara Solbak , Olle Nordesjö , Mikael Nissbeck , Daniel F.A.R. Dourado , Ken G. Andersson , Mohammad Reza Housaindokht , John Löfblom , Anders Virtanen , U. Helena Danielson , Samuel Coulbourn Flores ,

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Abstract

The interaction between the Staphylococcal Protein A (SpA) domain B (the basis of the Affibody) molecule and the Fc of IgG is key to the use of Affibodies in affinity chromatography and in potential therapies against certain inflammatory diseases. Despite its importance and fourdecade history, to our knowledge this interaction has never been affinity matured. We elucidate reasons why single-substitutions in the SpA which improve affinity to Fc may be very rare, and also discover substitutions which potentially serve several engineering purposes. We used a variation of FoldX to predict changes in protein–protein-binding affinity, and produce a list of 41 single-amino acid substitutions on the SpA molecule, of which four are near wild type (wt) and five are at most a factor of four from wt affinity. The nine substitutions include one which removes lysine, and several others which change charge. Subtle modulations in affinity may be useful for modifying column elution conditions. The method is applicable to other protein–protein systems, providing molecular insights with lower workload than existing experimental techniques.

Keywords

, affinity, computational prediction, protein-protein interactions, surface plasmon resonance, Staphylococcal Protein A
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@article{paperid:1062696,
author = {NOSRATI, MASOUMEH and Sara Solbak and Olle Nordesjö and Mikael Nissbeck and Daniel F.A.R. Dourado and Ken G. Andersson and Housaindokht, Mohammad Reza and John Löfblom and Anders Virtanen and U. Helena Danielson and Samuel Coulbourn Flores},
title = {Insights from engineering the Affibody-Fc interaction with a computational-experimental method},
journal = {Protein Engineering, Design and Selection},
year = {2017},
volume = {30},
number = {9},
month = {December},
issn = {1741-0126},
pages = {593--601},
numpages = {8},
keywords = {affinity; computational prediction; protein-protein interactions; surface plasmon resonance; Staphylococcal Protein A},
}

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%0 Journal Article
%T Insights from engineering the Affibody-Fc interaction with a computational-experimental method
%A NOSRATI, MASOUMEH
%A Sara Solbak
%A Olle Nordesjö
%A Mikael Nissbeck
%A Daniel F.A.R. Dourado
%A Ken G. Andersson
%A Housaindokht, Mohammad Reza
%A John Löfblom
%A Anders Virtanen
%A U. Helena Danielson
%A Samuel Coulbourn Flores
%J Protein Engineering, Design and Selection
%@ 1741-0126
%D 2017

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