TY - JOUR T1 - Interaction of N-3-Oxododecanoyl Homoserine Lactone with LasR protein of Pseudomonas aeruginosa: Insights from Molecular Docking and Dynamics Simulations JF - bioRxiv DO - 10.1101/121681 SP - 121681 AU - Hovakim Grabski AU - Lernik Hunanyan AU - Susanna Tiratsuyan AU - Hrachik Vardapetyan Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/28/121681.abstract N2 - In 2017 World Health Organization announced the list of the most dangerous superbugs and among them is Pseudomonas aeroginosa, which is an antibiotic resistant and opportunistic human pathogen. This organism attacks human patients suffering from such diseases as AIDS, cancer, cystic fibrosis, etc. Current therapies lack efficacy, partly because P.aeruginosa creates and inhabits surface-associated biofilms conferring increased resistance to antibiotics and host immune responses. There is an urgent requirement for novel antibacterial treatments to counter P. aeruginosa. However, till date the detailed molecular properties of the LasR protein are not clearly known. Therefore, in this work, an attempt has been made to analyze molecular properties of the LasR protein as well as the mode of its interactions with the N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL) autoinducer(AI). We analyzed the three-dimensional structure of the LasR protein of P. aeruginosa as well as performed docking and molecular dynamics (MD) simulations of the protein with the AI 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 turn in the vicinity of DNA binding domain of the protein was found. We have also performed LasR monomer protein docking and found a new form of dimerization. This study may, therefore, offer new insights for future experiments to determine the interaction of the autoinducer with the beta turn in the vicinity of DNA binding domain of LasR protein and a new interaction site for drug design.PDBProtein data bankMDMolecular DynamicsPCAPrincipal Component AnalysisPCPrincipal Component3-O-C12-HSLN-3-oxododecanoyl homoserine lactoneAIautoinducerBLASTBasic local alignment search toolDBIDavid-Bouldin IndexpsFpseudo-F statistic ER -