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.
Highlights
Measuring the structural distance or difference in proteins is crucial[26]
The joint-based descriptor was applied to quantify the conformational distance of the 7TM proteins from the GPCR A family, to examine the conformational difference between the active and inactive states of GPCR, and to validate the GPCR computational models
A prominent feature of the approach is to measure the structural distance at the macroscopic level, which permits an analysis of the conformational difference of complex proteins, such as TM proteins, in a more simplistic way
Summary
Measuring the structural distance or difference in proteins is crucial[26]. This is strongly related to the classification of proteins in nature, prediction of the protein structures, and the design of artificial proteins. A representative example is to estimate the structural distance of proteins using the Cα atom-based RMSD (Root Mean Square Deviation)[30,31,32,33]. Such microscopic descriptor-based approaches are effective in measuring the structural distance of proteins at the atomic level. The allowed and disallowed regions of their joint-based dihedral angles were examined, which provided information on the possible conformational space of the helical arrangement in TM proteins. A joint-based descriptor was applied to measure the conformational distance of helical TM proteins on a macroscopic level. The following three independent case studies were performed: (i) the approach was applied to identify how far the global and local conformations of the 7TM proteins in the PDB database are from the GPCR A family; (ii) the approach was used to validate the computational models of the GPCR structures at the joint-based coordinate level, and (iii) the approach was applied to study the conformational difference between the active and inactive states of the GPCR proteins
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