HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsOzlem Tastan Bishop, Matthys Kroon
JournalJournal of molecular modeling (J Mol Model) Vol. 17 Issue 12 Pg. 3163-72 (Dec 2011) ISSN: 0948-5023 [Electronic] Germany
PMID21365221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimalarials
  • Cysteine Proteinase Inhibitors
  • Cysteine Proteases
Topics
  • Amino Acid Sequence
  • Animals
  • Antimalarials (chemistry, metabolism, pharmacology)
  • Crystallography, X-Ray
  • Cysteine Proteases (chemistry, metabolism)
  • Cysteine Proteinase Inhibitors (chemistry, metabolism, pharmacology)
  • Databases, Protein
  • Humans
  • Malaria, Falciparum (drug therapy, parasitology)
  • Malaria, Vivax (drug therapy, parasitology)
  • Models, Molecular
  • Molecular Sequence Data
  • Plasmodium falciparum (enzymology)
  • Plasmodium vivax (enzymology)
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Thermodynamics

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: