1. Development of a quorum-sensing peptide database: Quorumpeps®
Evelien Wynendaele1, Antoon Bronselaer2, Guy De Tré2, Ewald Pauwels3,
Maxime Boucart1, Christophe Van de Wiele4 and Bart De Spiegeleer1,*
1 Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences; 2 Department of Telecommunications and Information Processing, Faculty of Engineering and Architecture; 3 Center for Molecular Modeling, Faculty of Sciences;
4 Department of Nuclear Medicine, Faculty of Medicine and Health Sciences; all Ghent University.
* Corresponding author: (O. Ref.: c)
1. INTRODUCTION
4. RESULTS
Quorum-sensing (QS) enables bacterial cells to establish cell-cell communication and to regulate the expression of specific genes in response to local changes in cell density. It provides a means to coordinate the activities of cells in order to function as a multicellular unit. Quorum-sensing chemicals up till now identified as key components in bacterial cell-cell communication can broadly be divided in three groups, which contain peptidic-derived structural characteristics: N-acyl homoserine lactone derivatives (auto-inducer-1), larger quorum-sensing peptides and boron-furanone derivatives (auto-inducer-2).
Clustering of quorum-sensing peptides:
Both PCA and HCA classified the quorum-sensing peptides in 4 main groups (Figure 2). Both the larger bacteriocins and lantibiotics are clustered in a separate group. The other groups contain several subclusters, which could be explained chemically and biologically.
Figure 2: Classification of quorum-sensing peptides using PCA
Bacteriocins
Lantibiotics
AIP, GBAP, EDF, ComX, Phr
CSP, BIP
2. EXPERIMENTAL
Quorumpeps®: a quorum-sensing peptide relational database
Structure
Functionality
Clustering:
Three-dimensional optimisation
Calculation of 3234 chem-informatic molecular descriptors
 1516 descriptors (without constants)
Preprocessing: autoscaling (z-score)
Multivariate analyses: Principal Component Analysis (PCA) and
Hiërarchical cluster analysis (HCA)
Chemical diversity
QSPR
3. RESULTS
Quorumpeps® database:
Figure 3: Subclusters containing AIP molecules … 1 12 13
N-Acyl homoserine lacton derivatives
Quorum-sensing
peptides
Boron-furanone derivatives
62 agonists
190 agonists
7 agonists
103 antagonists
57 antagonists
25 antagonists
Subclusters 1, 12 and 13 (Figure 3):
- Peptides bind to the AgrC receptor
- Characteristic thiolacton or lacton linkage
In separate subclusters, due to:
Subcluster 1: Mw (500 to 650 Da)
Subcluster 2: Mw (750 to 1000 Da) + pI (4.4) + logP (-1.3)
Subcluster 3: Mw (750 to 1000 Da) + pI (5.6 to 10.3) + logP (-3 to 7.7)
(End April 2011)
Figure 1: Quorumpeps® database: scheme
5. CONCLUSIONS
The database is a useful tool to justify peptide choices for evaluating different responses, studying quantitative structure-property relationships (QSPR) of quorum-sensing molecules or keeping informed of this expanding field.
6. REFERENCES
E. Wynendaele et al. Chemical clustering of quorum-sensing peptides through the Quorumpeps database. Publication in preparation
Soon available on web for other researchers!
Drug Quality & Registration (DruQuaR) format Man v01