Aggregation and network formation in self-assembly of protein (H3.1) by a coarse-grained Monte Carlo simulation

Abstract

Multi-scale aggregation to network formation of interacting proteins (H3.1) are examined by a knowledge-based coarse-grained Monte Carlo simulation as a function of temperature and the number of protein chains, i.e., the concentration of the protein. Self-assembly of corresponding homo-polymers of constitutive residues (Cys, Thr, and Glu) with extreme residue-residue interactions, i.e., attractive (Cys-Cys), neutral (Thr-Thr), and repulsive (Glu-Glu), are also studied for comparison with the native protein. Visual inspections show contrast and similarity in morphological evolutions of protein assembly, aggregation of small aggregates to a ramified network from low to high temperature with the aggregation of a Cys-polymer, and an entangled network of Glu and Thr polymers. Variations in mobility profiles of residues with the concentration of the protein suggest that the segmental characteristic of proteins is altered considerably by the self-assembly from that in its isolated state. The global motion of proteins and Cys polymer chains is enhanced by their interacting network at the low temperature where isolated chains remain quasi-static. Transition from globular to random coil transition, evidenced by the sharp variation in the radius of gyration, of an isolated protein is smeared due to self-assembly of interacting networks of many proteins. Scaling of the structure factor S(q) with the wave vector q provides estimates of effective dimension D of the mass distribution at multiple length scales in self-assembly. Crossover from solid aggregates (D ∼ 3) at low temperature to a ramified fibrous network (D ∼ 2) at high temperature is observed for the protein H3.1 and Cys polymers in contrast to little changes in mass distribution (D ∼ 1.6) of fibrous Glu- and Thr-chain configurations.

Self-assembly dynamics for the transition of a globular aggregate to a fibril network of lysozyme proteins via a coarse-grained Monte Carlo simulation

“…Such organized structures are believed to cause a number of neurodegenerative disorders (Alzheimer, Parkinson, Coronary heart, etc.). [1][2][3][4][5][6][7][8][9][10][11][12] Many different human proteins such as beta-amyloid, alpha-synuclein, lysozyme, and insulin, with different sequences and structures can form insoluble amyloid fibrils with somewhat similar morphology. 13 Enormous efforts have been made in attempting to understanding the underlying mechanisms.…”

“…Therefore, simplifications via appropriate coarse-grained approximations is necessary. Using a coarse-grained approach 5 we investigate the self-organizing structures of lysozyme C ( 1 M 2 K 3 A . .…”

“…Investigating the structural transitions with simulations that involve many proteins, solvent, and a host of other constitutive elements is even more challenging. [1][2][3][4][5] In order to study the self-organizing structures involved in fibril formation, aggregation, dispersion, etc. resulting from the cooperative and competing mechanisms, one has to consider many proteins in a matrix.…”

“…With the large-scale simulations, they have identified the appearance of a range of morphologies e.g from a solid-aggregate at low temperatures to the onset of long-range fibrous networks at high temperatures as a function of protein density. Using the same coarse-grained method, 5 we study the multi-scale morphology of lysozyme as a function of temperature and concentration. The model is presented in the next section, followed by results and discussion with a concluding remark towards the end.…”

“…27 peptides each with 7 residues to study fibrils, β-barrel, and aggregate structures). 2 Using a coarse-grained Monte Carlo simulation, Pandey and Farmer 5 have recently examined the multi-scale structures in self-assembly of histones (H3.1, a protein with 136 residues) with as many as 20 proteins in the simulation box. With the large-scale simulations, they have identified the appearance of a range of morphologies e.g from a solid-aggregate at low temperatures to the onset of long-range fibrous networks at high temperatures as a function of protein density.…”