title: Interaction of malaria parasite-inhibitory antibodies with the merozoite surface protein MSP1(19) by computational docking.
abstract: Merozoite surface protein 1 (MSP1) of the malaria parasite Plasmodium falciparum is an important vaccine candidate antigen. Antibodies specific for the C-terminal maturation product, MSP1(19), have been shown to inhibit erythrocyte invasion and parasite growth. Specific monoclonal antibodies react with conformational epitopes contained within the two EGF-like domains that constitute the antigen MSP1(19). To gain greater insight into the inhibitory process, the authors selected two strongly inhibitory antibodies (designated 12.8 and 12.10) and modeled their structures by homology. Computational docking was used to generate antigen-antibody complexes and a selection filter based on NMR data was applied to obtain plausible models. Molecular Dynamics simulations of the selected complexes were performed to evaluate the role of specific side chains in the binding. Favorable complexes were obtained that complement the NMR data in defining specific binding sites. These models can provide valuable guidelines for future experimental work that is devoted to the understanding of the action mechanism of invasion-inhibitory antibodies.
authors.affiliation: Dipartimento di Chimica Organica e Biochimica, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, via Cinthia, 80126, Naples, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Autore
authors.forename: Sara
authors.initials: S
authors.lastname: Melchiorre
authors.forename: Jens
authors.initials: J
authors.lastname: Kleinjung
authors.forename: William D
authors.initials: WD
authors.lastname: Morgan
authors.forename: Franca
authors.initials: F
authors.lastname: Fraternali
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex; D003198:Computer Simulation; D006801:Humans; D008288:Malaria / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D010961:Plasmodium / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000913:Antibodies, Protozoan; D000936:Antigen-Antibody Complex; D020066:Merozoite Surface Protein 1