title: Modeling the LPS neutralization activity of anti-endotoxins.
abstract: Bacterial lipopolysaccharides (LPS), also known as endotoxins, are major structural components of the outer membrane of Gram-negative bacteria that serve as a barrier and protective shield between them and their surrounding environment. LPS is considered to be a major virulence factor as it strongly stimulates the secretion of pro-inflammatory cytokines which mediate the host immune response and culminating in septic shock. Quantitative structure-activity relationship studies of the LPS neutralization activities of anti-endotoxins were performed using charge and quantum chemical descriptors. Artificial neural network implementing the back-propagation algorithm was selected for the multivariate analysis. The predicted activities from leave-one-out cross-validation were well correlated with the experimental values as observed from the correlation coefficient and root mean square error of 0.930 and 0.162, respectively. Similarly, the external testing set also yielded good predictivity with correlation coefficient and root mean square error of 0.983 and 0.130. The model holds great potential for the rational design of novel and robust compounds with enhanced neutralization activity.
authors.affiliation: Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
authors.forename: Chadinee
authors.initials: C
authors.lastname: Thippakorn
authors.forename: Thummaruk
authors.initials: T
authors.lastname: Suksrichavalit
authors.forename: Chanin
authors.initials: C
authors.lastname: Nantasenamat
authors.forename: Tanawut
authors.initials: T
authors.lastname: Tantimongcolwat
authors.forename: Chartchalerm
authors.initials: C
authors.lastname: Isarankura-Na-Ayudhya
authors.forename: Thanakorn
authors.initials: T
authors.lastname: Naenna
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000276:immunology; D004731:Endotoxins / Q000737:chemistry / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides