title: Homology modelling of annexin I: implicit solvation improves side-chain prediction and combination of evaluation criteria allows recognition of different types of conformational error.
abstract: Annexin I homology models were built from the annexin V crystal structure. Three methods for side-chain prediction were tested based on molecular mechanics conformational search, the use of a rotamer database, or a combination of these two methods. We showed that rotamer-based methods were more efficient and that molecular mechanics energy minimizations, prior to rotamer selection, did not afford clearly improved predictions. Models built in vacuo and with an implicit solvation term were compared with the annexin I crystal structure which became available during the course of this study. The analysis of solvation energies, root mean square deviations, chi 1 angles and hydrogen bonds showed that models built with implicit solvation were of better quality. In annexin V, repeat III displays A-B and D-E loop conformations quite different from other repeats. Since the sequence differences suggest that repeat III in annexin I might present a conformation similar to other repeats, two annexin I models with different repeat III conformations were built and compared to determine whether the correct conformation could have been predicted. We show that using a combination of evaluation criteria, it is possible to discriminate unequivocally between the native and the incorrect fold, stressing that only one criterion should not be used to evaluate protein structures.
authors.affiliation: Centre de Biochimie Structurale CNRS-INSERM, Faculté de Pharmacie, Université Montpellier I, France.
authors.forename: D
authors.initials: D
authors.lastname: Cregut
authors.forename: J P
authors.initials: JP
authors.lastname: Liautard
authors.forename: L
authors.initials: L
authors.lastname: Chiche
mesh_terms: D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000737:chemistry*; D017318:Annexin A3 / Q000737:chemistry; D017304:Annexin A5 / Q000737:chemistry; D003198:Computer Simulation; D003461:Crystallography; D016208:Databases, Factual; D005069:Evaluation Studies as Topic; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry
chemical_list: D017305:Annexin A1; D017304:Annexin A5; D014867:Water; D017318:Annexin A3