چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده ثبت کننده مقاله | سیاوش دستمالچی |
| مرحله جاری مقاله | تایید نهایی |
| دانشکده/مرکز مربوطه | مرکز تحقیقات بیوتکنولوژی(زیست فناوری) |
| کد مقاله | 59383 |
| عنوان فارسی مقاله | Modelling the structures of G protein-coupled receptors aided by three-dimensional validation |
| عنوان لاتین مقاله | Modelling the structures of G protein-coupled receptors aided by three-dimensional validation |
| ناشر | 3 |
| آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ | بلی |
| عنوان نشریه (خارج از لیست فوق) | |
| نوع مقاله | Original Article |
| نحوه ایندکس شدن مقاله | ایندکس شده سطح یک – ISI - Web of Science |
| آدرس لینک مقاله/ همایش در شبکه اینترنت | https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-9-S1-S14 |
| Background: G protein-coupled receptors (GPCRs) are abundant, activate complex signalling and represent the targets for up to ~60% of pharmaceuticals but there is a paucity of structural data. Bovine rhodopsin is the first GPCR for which high-resolution structures have been completed but significant variations in structure are likely to exist among the GPCRs. Because of this, considerable effort has been expended on developing in silico tools for refining structures of individual GPCRs. We have developed REPIMPS, a modification of the inverse-folding software Profiles-3D, to assess and predict the rotational orientation and vertical position of helices within the helix bundle of individual GPCRs. We highlight the value of the method by applying it to the Baldwin GPCR template but the method can, in principle, be applied to any low- or high-resolution membrane protein template or structure. Results: 3D models were built for transmembrane helical segments of 493 GPCRs based on the Baldwin template, and the models were then scored using REPIMPS and Profiles-3D. The compatibility scores increased significantly using REPIMPS because it takes into account the physicochemical properties of the (lipid) environment surrounding the helix bundle. The arrangement of helices in the helix bundle of the 493 models was then altered systematically by rotating the individual helices. For most GPCRs in the set, changes in the rotational position of one or more helices resulted in significant improvement in the compatibility scores. In particular, for most GPCRs, a rotation of helix VII by 240–300° resulted in improved scores. Bovine rhodopsin modelled using this method showed 3.31 Å RMSD to its crystal structure for 198 C α atom pairs, suggesting the utility of the method even when starting with idealised structures such as the Baldwin template. Conclusion: We have developed an in silico tool which can be used to test the validity of, and refine, models of GPCRs with respect to helix rotation and vertical position based on the physicochemical properties of amino acids and the surrounding environment. The method can be applied to any multi-pass membrane protein and potentially can be used in combination with other high-throughput methodologies to generate and refine models of membrane proteins. |
| نویسنده | نفر چندم مقاله |
|---|---|
| سیاوش دستمالچی | اول |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| 48.pdf | 1395/08/27 | 1289292 | دانلود |
