title: Study of protein complexes via homology modeling, applied to cysteine proteases and their protein inhibitors.
abstract: This paper develops and evaluates large-scale calculation of 3D structures of protein complexes by homology modeling as a promising new approach for protein docking. The complexes investigated were papain-like cysteine proteases and their protein inhibitors, which play numerous roles in human and parasitic metabolisms. The structural modeling was performed in two parts. For the first part (evaluation set), nine crystal structure complexes were selected, 1325 homology models of known complexes were rebuilt by various templates including hybrids, allowing an analysis of the factors influencing the accuracy of the models. The important considerations for modeling the interface were protease coverage and inhibitor sequence identity. In the second part (study set), the findings of the evaluation set were used to select appropriate templates to model novel cysteine protease-inhibitor complexes from human and malaria parasites Plasmodium falciparum and Plasmodium vivax. The energy scores, considering the evaluation set, indicate that the models are of high accuracy.
authors.affiliation: Rhodes University Bioinformatics (RUBi), Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown 6140, South Africa. o.tastanbishop@ru.ac.za
authors.forename: Ozlem
authors.initials: O
authors.lastname: Tastan Bishop
authors.forename: Matthys
authors.initials: M
authors.lastname: Kroon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D057056:Cysteine Proteases / Q000737:chemistry / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D030562:Databases, Protein; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D016780:Malaria, Vivax / Q000188:drug therapy / Q000469:parasitology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology*; D010966:Plasmodium vivax / Q000201:enzymology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
chemical_list: D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D057056:Cysteine Proteases