title: Impact of I30T and I30M substitution in MPZ gene associated with Dejerine-Sottas syndrome type B (DSSB): A molecular modeling and dynamics.
abstract: Myelin protein zero (MPZ) gene encodes MPZ protein is a vital component of the myelin sheath. Mutationsassociated with MPZ gene leads to severe de-hypomyelination Dejerine-Sottas syndrome type B (DSSB) also termed as Charcot-Marie-Tooth disease (CMT) type 3. In this work, we employed a set of various in silico prediction methods to screen 97 nsSNPs associated with MPZ gene. Based on this, we identified the nsSNPs to be most deleterious and pathogenic associated with DSSB. To get more insight into the mutational effect at three-dimensional structural level, we modeled the homology structure of native type as well as I30T and I30M mutant of MPZ protein using Modeler 9.13 software. Molecular dynamics simulation was initiated to explain the impact of the mutation on its structure and function. The obtained results depict that the protein with I30T mutation had variable structural conformation and dynamic behavior than native and mutant I30M of MPZ protein. We hope our computational insight might be helpful in rationalizing the deleterious mutations in DSSB and the advancement of novel pharmacological strategy.
authors.affiliation: Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Agrahari
authors.affiliation: Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India. Electronic address: georgepriyadoss@vit.ac.in.
authors.forename: C
authors.initials: C
authors.lastname: George Priya Doss
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003198:Computer Simulation; D017124:Conserved Sequence; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D018993:Myelin P0 Protein / Q000737:chemistry / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017433:Protein Structure, Secondary
chemical_list: D050505:Mutant Proteins; D018993:Myelin P0 Protein
keywords: DSSB; I30M; I30T; MPZ; Molecular dynamics; nsSNPs