Disordered peptide chains in an α-C-based coarse-grained model

Abstract

We construct a one-bead-per-residue coarse-grained dynamical model to describe intrinsically disordered proteins at significantly longer timescales than in the all-atom models. In this model, inter-residue contacts form and disappear during the course of the time evolution. The contacts may arise between the sidechains, the backbones or the sidechains and backbones of the interacting residues. The model yields results that are consistent with many all-atom and experimental data on these systems. We demonstrate that the geometrical properties of various homopeptides differ substantially in this model. In particular, the average radius of gyration scales with the sequence length in a residue-dependent manner.

Gō model revisited

“…Hoang, T. X., et al proposed to use three consecutive Cα positions to calculate orientations of backbone amide-and carbonyl-groups of the central residue so that the orientation-dependent backbone hydrogen bonds can be modeled as a function of 6 Cα coordi nates, which was carefully calibrated later [56,57]. A similar approach was further developed to model the sidechain orientation in terms of three consecutive Cα positions [58,59]. This type of modeling is particularly useful to model intrinsically disorder proteins/regions that lack the native structure, as well as amyloid like higher-order structures.…”

Ameliorating amyloid aggregation through osmolytes as a probable therapeutic molecule against Alzheimer's disease and type 2 diabetes

“…Various modeled peptides have been considered as IDPs, showing completely diverse properties except for all having organized 3D structures [84][85][86] . Both Ab and hIAPP in the presence of G-HCL and L-PRO showed various conformational ensembles of structures that interconvert simultaneously.…”

Networks of interbasin traffic in intrinsically disordered proteins

“…The latter are the structured lysozyme (PDB:2LYZ; N = 129) and the disordered [22,23] α-synuclein (N = 140), the protein that is associated with Parkinson's disease [24,25]. These proteins are studied by the recently proposed α-C based coarse-grained (CG) model [26] (that is more protein specific than that used in Ref. [27]) and by all-atom (AA) NAMD-based simulations [28] with the implicit solvent and the CHARMM36m [29] force field designed for the IDPs.…”

“…There is one change relative to the description provided in Ref. [26]: attractive electrostatic interactions are now treated as other sidechain-sidechain contacts (if the proper conditions are met) instead of being described by the modified Debye-Huckel potential. This correction enhances the agreement with experimental data for charged proteins.…”

“…The CG model [26] is defined in terms of ε-the depth of the Lennard-Jones potential well associated with the contact. The room temperature situation corresponds to k B T /ε ≈ 0.35, where k B is the Boltzmann constant.…”