Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, EpiSciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Conformational and docking studies of acyl homoserine lactones as a robust method to investigate bioactive conformations

Laurent Soulère 1 yves Queneau 1 
1 COB - Chimie Organique et Bioorganique
ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
Abstract : A method aiming at investigating possible bioactive conformations of acyl homoserine lactone (AHL) quorum sensing (QS) modulators is established. The method relies on the exhaustive conformational analysis of AHLs by varying torsion angles around the amide group then on the selection of the closest conformation to those known from co-crystallized XRD data of AHL-receptor complexes. These latter are then docked as rigid ligand within the receptor binding site, leading to interactions with binding site residues which are highly consistent as compared with the data arising from XRD studies. The method is first validated using AHLs for which XRD data of their complexes with their cognate receptor are available, then extended to examples for which the binding mode is still unknown. Three compounds were used to validate the method: hexanoyl homoserine lactone (HHL) as an example of autoinducer, 3-oxo-butanoyl homoserine lactone (OBHL), as a representative model of 3-oxo-AHLs, and 4-(4-chlorophenoxy)butanoyl homoserine lactone (CPOBHL) as an example of a QS inhibitor. The conformational analysis of these three compounds to their cognate protein (TraR, SdiA, LasR and CviR) provides the data which enable the next rigid docking step. Further rigid docking of the closest conformations compared to the known bioactive ones within the binding sites allows to recover the expected binding mode with high precision (atomic RMSD < 2 Å). This "conformational analysis/torsion angle filter/rigid ligand docking" method was then used for investigating three non-natural AHL-type QS inhibitors without known co-crystallized XRD structures, namely was 2-hexenoyl homoserine lactone (HenHL), 3-oxo-4-phenylbutanoyl homoserine lactone (OPBHL) and 3-(4-bromophenyl)propanoyl homoserine lactone (BPPHL). Results provide insights into their possible binding mode by identifying specific interactions with some key residues within the receptor binding site, allowing discussion of their biological activity.
Document type :
Journal articles
Complete list of metadata

Cited literature [31 references]  Display  Hide  Download
Contributor : UMR5246 ICBMS Connect in order to contact the contributor
Submitted on : Thursday, July 9, 2020 - 11:42:33 AM
Last modification on : Sunday, June 26, 2022 - 2:51:47 AM
Long-term archiving on: : Monday, November 30, 2020 - 5:34:38 PM


Comput Biol CHem 2019.pdf
Files produced by the author(s)



Laurent Soulère, yves Queneau. Conformational and docking studies of acyl homoserine lactones as a robust method to investigate bioactive conformations. Computational Biology and Chemistry, Elsevier, 2019, 79, pp.48-54. ⟨10.1016/j.compbiolchem.2019.01.006⟩. ⟨hal-02110869⟩



Record views


Files downloads