RT Journal Article SR Electronic T1 Interaction of N-3-oxododecanoyl homoserine lactone with transcriptional regulator LasR of Pseudomonas aeruginosa: Insights from molecular docking and dynamics simulations JF bioRxiv FD Cold Spring Harbor Laboratory SP 121681 DO 10.1101/121681 A1 Hovakim Grabski A1 Lernik Hunanyan A1 Susanna Tiratsuyan A1 Hrachik Vardapetyan YR 2017 UL http://biorxiv.org/content/early/2017/06/12/121681.abstract AB In 2017 World Health Organization announced the list of the most dangerous superbugs and among them is Pseudomonas aeruginosa, which is an antibiotic resistant opportunistic human pathogen. The central problem is that it affects patients suffering from AIDS, cystic fibrosis, cancer, burn victims etc. P. aeruginosa creates and inhabits surface-associated biofilms. Biofilms increase resistance to antibiotics and host immune responses, because of that current treatments are not effective. It is imperative to find new antibacterial treatment strategies against P. aeruginosa, but detailed molecular properties of the LasR protein are not clearly known to date. In the present study we tried to analyze the molecular properties of the LasR protein as well as the mode of its interactions with autoinducer (AI) the N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL). We performed docking and molecular dynamics (MD) simulations of the LasR protein of P. aeruginosa with the 3-O-C12-HSL ligand. We assessed the conformational changes of the interaction and analyzed the molecular details of the binding of the 3-O-C12-HSL with LasR. A new interaction site of the 3-O-C12-HSL with the beta turns in the short linker region (SLR) of LasR protein was found. We have also performed LasR monomer protein docking and found a new form of dimerization. This study may offer new insights for future experimental studies to detect the interaction of the autoinducer with the beta turns in the short linker region (SLR) of LasR protein and a new interaction site for drug design.