Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/113723
Title: Ligand's Partition to the Lipid Bilayer Should Be Accounted for When Estimating Their Affinity to Proteins
Authors: Moreno, Maria João 
Salvador, Armindo 
Keywords: binding affinity; partition coefficient; membrane proteins; lipid-protein ratio; ligand sequestration; ligand exclusion; protein specificity
Issue Date: 31-Mar-2023
Publisher: MDPI
Project: UIDB/04539/2020 
UIDP/04539/2020 
LA/P/0058/2020 
UIDB/00313/2020 
UIDP/00313/2020 
Serial title, monograph or event: Molecules
Volume: 28
Issue: 7
Abstract: Ligand-protein interactions are usually studied in complex media that also contain lipids. This is particularly relevant for membrane proteins that are always associated with lipid bilayers, but also for water-soluble proteins studied in in vivo conditions. This work addresses the following two questions: (i) How does the neglect of the lipid bilayer influence the apparent ligand-protein affinity? (ii) How can the intrinsic ligand-protein affinity be obtained? Here we present a framework to quantitatively characterize ligand-protein interactions in complex media for proteins with a single binding site. The apparent affinity obtained when following some often-used approximations is also explored, to establish these approximations' validity limits and to allow the estimation of the true affinities from data reported in literature. It is found that an increase in the ligand lipophilicity or in the volume of the lipid bilayer always leads to a decrease in the apparent ligand-protein affinity, both for water-soluble and for membrane proteins. The only exceptions are very polar ligands (excluded from the lipid bilayer) and ligands whose binding affinity to the protein increases supralinearly with ligand lipophilicity. Finally, this work discusses which are the most relevant parameters to consider when exploring the specificity of membrane proteins.
URI: https://hdl.handle.net/10316/113723
ISSN: 1420-3049
DOI: 10.3390/molecules28073136
Rights: openAccess
Appears in Collections:IIIUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
I&D CQC - Artigos em Revistas Internacionais
FCTUC Química - Artigos em Revistas Internacionais

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This item is licensed under a Creative Commons License Creative Commons