Monte Carlo studies of protein aggregation

• The disease-linked amyloid beta (A beta) and alpha-synuclein (alpha S) proteins are both fibril-forming and natively unfolded in free monomeric form. Here, we discuss two recent studies, where we used extensive implicit solvent all-atom Monte Carlo (MC) simulations to elucidate the conformational ensembles sampled by these proteins. For alpha S, we somewhat unexpectedly observed two distinct phases, separated by a clear free-energy barrier. The presence of the barrier makes alpha S, with 140 residues, a challenge to simulate. By using a two-step simulation procedure based on flat-histogram techniques, it was possible to alleviate this problem. The barrier may in part explain why fibril formation is much slower for alpha S than it is for A beta.

Ämnesord

NATURVETENSKAP  -- Fysik -- Subatomär fysik (hsv//swe)

NATURAL SCIENCES  -- Physical Sciences -- Subatomic Physics (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biofysik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biophysics (hsv//eng)

Nyckelord

protein misfolding

protein aggregation

amyloid

Publikations- och innehållstyp

kon (ämneskategori)

ref (ämneskategori)