Homology modeling of an RNP domain from a human RNA-binding protein: Homology-constrained energy optimization provides a criterion for distinguishing potential sequence alignments

Parag V. Sahasrabudhe, Roberto Tejero, Saori Kitao, Yasuhiro Furuichi, Gaetano T. Montelione

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

We have recently described an automated approach for homology modeling using restrained molecular dynamics and simulated annealing procedures (Li et al, Protein Sci., 6:956-970,1997). We have employed this approach for constructing a homology model of the putative RNA-binding domain of the human RNA-binding protein with multiple splice sites (RBP-MS). The regions of RBP- MS which are homologous to the template protein snRNP U1A were constrained by 'homology distance constraints,' while the conformation of the non-homologous regions were defined only by a potential energy function. A full energy function without explicit solvent was employed to ensure that the calculated structures have good conformational energies and are physically reasonable. The effects of misalignment of the unknown and the template sequences were also explored in order to determine the feasibility of this homology modeling method for distinguishing possible sequence alignments based on considerations of the resuiting conformational energies of modeled structures. Differences in the alignments of the unknown and the template sequences result in significant differences in the conformational energies of the calculated homology models. These results suggest that conformational energies and residual constraint violations in these homology-constrained simulated annealing calculations can be used as criteria to distinguish between correct and incorrect sequence alignments and chain folds.

Original languageEnglish (US)
Pages (from-to)558-566
Number of pages9
JournalProteins: Structure, Function and Genetics
Volume33
Issue number4
DOIs
StatePublished - Dec 1 1998

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Keywords

  • Drosophila melanogaster couch potato protein
  • Restrained molecular dynamics
  • Simulated annealing
  • Werner's syndrome

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