Kaczor, Agnieszka A. and Guixa-Gonzalez, Ramon and Carrio, Pau and Poso, Antti and Dove, Stefan and Pastor, Manuel and Selent, Jana (2015) Multi-Component Protein - Protein Docking Based Protocol with External Scoring for Modeling Dimers of G Protein-Coupled Receptors. MOLECULAR INFORMATICS, 34 (4). pp. 246-255. ISSN 1868-1743, 1868-1751
Full text not available from this repository. (Request a copy)Abstract
In order to apply structure-based drug design techniques to GPCR complexes, it is essential to model their 3D structure. For this purpose, a multi-component protocol was derived based on protein-protein docking which generates populations of dimers compatible with membrane integration, considering all reasonable interfaces. At the next stage, we applied a scoring procedure based on up to eleven different parameters including shape or electrostatics complementarity. Two methods of consensus scoring were performed: (i) average scores of 100 best scored dimers with respect to each interface, and (ii) frequencies of interfaces among 100 best scored dimers. In general, our multi-component protocol gives correct indications for dimer interfaces that have been observed in X-ray crystal structures of GPCR dimers (opsin dimer, chemokine CXCR4 and CCR5 dimers, kappa opioid receptor dimer, beta(1) adrenergic receptor dimer and smoothened receptor dimer) but also suggests alternative dimerization interfaces. Interestingly, at times these alternative interfaces are scored higher than the experimentally observed ones suggesting them to be also relevant in the life cycle of studied GPCR dimers. Further results indicate that GPCR dimer and higher-order oligomer formation may involve transmembrane helices (TMs) TM1-TM2-TM7, TM3-TM4-TM5 or TM4-TM5-TM6 but not TM1-TM2-TM3 or TM2-TM3-TM4 which is in general agreement with available experimental and computational data.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MOLECULAR-DYNAMICS; OPIOID RECEPTOR; SURFACE-ROUGHNESS; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; OLIGOMERIZATION; DIMERIZATION; HETERODIMERIZATION; SIMULATIONS; TRANSMEMBRANE; Docking; Protein - protein interactions; Protein modeling |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2019 14:08 |
| Last Modified: | 22 Jul 2019 14:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5725 |
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