Improving homology modeling from low-sequence identity templates in Rosetta: A case study in GPCRs.

ABSTRACT: As sequencing methodologies continue to advance, the availability of protein sequences far outpaces the ability of structure determination. Homology modeling is used to bridge this gap but relies on high-identity templates for accurate model building. G-protein coupled receptors (GPCRs) represent a significant target class for pharmaceutical therapies in which homology modeling could fill the knowledge gap for structure-based drug design. To date, only about 17% of druggable GPCRs have had their structures characterized at atomic resolution. However, modeling of the remaining 83% is hindered by the low sequence identity between receptors. Here we test key inputs in the model building process using GPCRs as a focus to improve the pipeline in two critical ways: Firstly, we use a blended sequ

SUBMITTER: Bender BJ 

PROVIDER: S-EPMC7652349 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature