Abstract：
:Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of "refined restraints first, modeling next", provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Chaudhari R,Heim AJ,Li Zdoi
10.1007/s10822-014-9823-2subject
Has Abstractpub_date
2015-05-01 00:00:00pages
413-20issue
5eissn
0920-654Xissn
1573-4951journal_volume
29pub_type
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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