title: In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ).
abstract: Human STIL (SCL/TAL1 interrupting locus) protein maintains centriole stability and spindle pole localisation. It helps in recruitment of CENPJ (Centromere protein J)/CPAP (centrosomal P4.1-associated protein) and other centrosomal proteins. Mutations in STIL protein are reported in several disorders, especially in deregulation of cell cycle cascades. In this work, we examined the non-synonymous single nucleotide polymorphisms (nsSNPs) reported in STIL protein for their disease association. Different SNP prediction tools were used to predict disease-associated nsSNPs. Our evaluation technique predicted rs147744459 (R242C) as a highly deleterious disease-associated nsSNP and its interaction behaviour with CENPJ protein. Molecular modelling, docking and molecular dynamics simulation were conducted to examine the structural consequences of the predicted disease-associated mutation. By molecular dynamic simulation we observed structural consequences of R242C mutation which affects interaction of STIL and CENPJ functional domains. The result obtained in this study will provide a biophysical insight into future investigations of pathological nsSNPs using a computational platform.
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu, India.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
authors.forename: Vidya
authors.initials: V
authors.lastname: Rajendran
authors.forename: Rao
authors.initials: R
authors.lastname: Sethumadhavan
authors.forename: Rituraj
authors.initials: R
authors.lastname: Purohit
keywords: CENPJ protein; CENPJ, Centromere protein J; Docking; ED, Essential dynamics; MDS, Molecular dynamics simulation; Molecular dynamics simulation; NHbonds, Number of hydrogen bonds; RMSD, Root-mean-square deviation; RMSF, Root-mean square fluctuation; Rg, Radius of gyration; SASA, Solvent-accessible surface area; STIL protein; STIL, SCL/TAL1 interrupting locus; nsSNPs, non-synonymous single nucleotide polymorphisms