Uncovering the potential basis of the structural and functional glitches of VRQPrP

Altered physiologic function of prion is one of the proposed mechanisms of neurodegeneration through perturbed activities of PrPC.Experimental studies reported the link between sequence variation in the functional domains of prion protein and scrapie disease development .This study highlights how variants could potentially affect the prion protein dynamics i.e. conformational flexibility, ligand binding affinity, solvent accessibility and probability score of amyloid forming hotspot sequences. Secondary structures were predicted using The MINNUS server-POLYVIEW-2D.3D structure Residue specific ligand binding probability and secondary structure were predicted using I-Tasser online server.SDM prediction pipeline to assess the potential effect of variants. Amyloidogenicity propensity of hotspot heptapeptides were predicted using Multiple Instance Learning Based Amyloid Prediction (MILAMP) online pipeline VRQ PrP diplayed broken helix flanked by strand and it has has more strand percentage than ARR PrP.All hotspot sequences containing the resistant variant at 136 and 171 codons were predicted to have lower amyloid propensity.The ligand residue was predicted to be buried in VRQ but exposed in ARR