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Interaction of malaria parasite‐inhibitory antibodies with the merozoite surface protein MSP1 19 by computational docking
Author(s) -
Autore Flavia,
Melchiorre Sara,
Kleinjung Jens,
Morgan William D.,
Fraternali Franca
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21212
Subject(s) - plasmodium falciparum , monoclonal antibody , docking (animal) , epitope , antibody , homology modeling , antigen , biology , computational biology , malaria , chemistry , microbiology and biotechnology , biochemistry , immunology , enzyme , medicine , nursing
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. Proteins 2007. © 2006 Wiley‐Liss, Inc.