Measuring the Conformational Distance of GPCR-related Proteins Using a Joint-based Descriptor

Abstract

Joint-based descriptor is a new level of macroscopic descriptor for protein structure using joints of secondary structures as a basic element. Here, we propose how the joint-based descriptor can be applied to examine the conformational distances or differences of transmembrane (TM) proteins. Specifically, we performed three independent studies that measured the global and conformational distances between GPCR A family and its related structures. First, the conformational distances of GPCR A family and other 7TM proteins were evaluated. This provided the information on the distant and close families or superfamilies to GPCR A family and permitted the identification of conserved local conformations. Second, computational models of GPCR A family proteins were validated, which enabled us to estimate how much they reproduce the native conformation of GPCR A proteins at global and local conformational level. Finally, the conformational distances between active and inactive states of GPCR proteins were estimated, which identified the difference of local conformation. The proposed macroscopic joint-based approach is expected to allow us to investigate structural features, evolutionary relationships, computational models and conformational changes of TM proteins in a more simplistic manner.

Comparative Analysis of TM and Cytoplasmic β-barrel Conformations Using Joint Descriptor

“…Like TM helical proteins, a set of joints connecting the individual β-strands and loops were selected to describe a β-barrel geometry based on the joint-based description approach. Specifically, the Cα carbon coordinates of the first and last residues of each β-strand were considered as structural joining points as they represent the basic elements of protein structures 37 , 38 . The spatial arrangement of such joint points was measured by the dihedral angles between them.…”

“…For the comparative analysis of TM β-barrels with cytoplasmic structures, the joint-derived dihedral angles of β-strands were used. The β-γ dihedral angles are macroscopic descriptions of protein structures based on joint-based approach 37 , 38 . In both cases, specific allowed and disallowed conformational accessible spaces were found.…”

“…In the present study, we attempted to perform a systematic comparison of β-barrels TM and β-barrels cytoplasm geometries using the joint-based description approach 37 , 38 . For comparison, structures of high-resolution, non-homologous β-barrels TM and β-barrels cytoplasm protein structures were obtained from the PDB and grouped based on their geometric analyses.…”