Interplay of sequence, topology and termini charge in determining the stability of the aggregates of GNNQQNY mutants: a molecular dynamics study.

ABSTRACT: This study explores the stabilities of single sheet parallel systems of three sequence variants of 1GNNQQNY7, N2D, N2S and N6D, with variations in aggregate size (5-8) and termini charge (charged or neutral). The aggregates were simulated at 300 and 330 K. These mutations decrease amyloid formation in the yeast prion protein Sup35. The present study finds that these mutations cause instability even in the peptide context. The protonation status of termini is found to be a key determinant of stabilities; other determinants are sequence, position of mutation and aggregate size. All systems with charged termini are unstable, whereas both stable and unstable systems are found when the termini are neutral. When termini are charged, the largest stable aggregate for the N2S and N6D systems has 3

SUBMITTER: Srivastava A 

PROVIDER: S-EPMC4015988 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature