A computational approach for mining cholesterol and their potential target against GPCR seven helices based on spectral clustering and fuzzy c-means algorithms

Abstract

In modern biology, GPCRs occupy a solitary crossroad and it signifies as important families of membrane receptors. In human body, all intracellular communications and cell signaling can take place with the knowledge of GPCR protein. Cholesterol is a vital sterol that is requisite for cell development and differentiation in mammalian cells. Modulating the function of several membrane proteins membrane cholesterol plays a significant role. Among these proteins, a particular cholesterol binding motif is reported to which the membrane cholesterol binds and modulates their movement. This consensus motif is either seen as CRAC and CARC, which correspond to any amino acid between one and five residues. Therefore, the recent work is focused on human GPCR transporters to identify the allocation of this motif in all seven helices of GPCR family and provide a harmony signature motif for an individual helix. A computational approach based on Spectral Clustering using Fuzzy c-Means has been experimented to obtain heterogeneous type of sequence for cholesterol from GPCR super family. From the obtained result, it is seen that excluding olfactory family in our dataset we found perfect matching of cholesterol motif with Transmembrane helices of GPCR family which can be further extended to other membrane proteins.

Keywords

GPCR spectral clustering FCM transmembrane helix (TM)CARC CRAC

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