TY  - JOUR
AU  - Ilie, I.
AU  - den Otter, W. K.
AU  - Briels, Willem
TI  - A coarse grained protein model with internal degrees of freedom. Application to α-synuclein aggregation
JO  - The journal of chemical physics
VL  - 144
IS  - 8
SN  - 1089-7690
CY  - Melville, NY
PB  - American Institute of Physics
M1  - FZJ-2016-00256
SP  - 085103
PY  - 2016
AB  - Particles in simulations are traditionally endowed with fixed interactions. While this is appropriate for particles representing atoms or molecules, objects with significant internal dynamics—like sequences of amino acids or even an entire protein—are poorly modelled by invariable particles. We develop a highly coarse grained polymorph patchy particle with the ultimate aim of simulating proteins as chains of particles at the secondary structure level. Conformational changes, e.g., a transition between disordered and β-sheet states, are accommodated by internal coordinates that determine the shape and interaction characteristics of the particles. The internal coordinates, as well as the particle positions and orientations, are propagated by Brownian Dynamics in response to their local environment. As an example of the potential offered by polymorph particles, we model the amyloidogenic intrinsically disordered proteinα-synuclein, involved in Parkinson’s disease, as a single particle with two internal states. The simulations yield oligomers of particles in the disordered state and fibrils of particles in the “misfolded” cross-β-sheet state. The aggregationdynamics is complex, as aggregates can form by a direct nucleation-and-growth mechanism and by two-step-nucleation through conversions between the two cluster types. The aggregationdynamics is complex, with fibrils formed by direct nucleation-and-growth, by two-step-nucleation through the conversion of an oligomer and by auto-catalysis of this conversion.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000371618800056
C6  - pmid:26931727
DO  - DOI:10.1063/1.4942115
UR  - https://juser.fz-juelich.de/record/280486
ER  -