Thermodynamics and Conformations of Single Polyalanine, Polyserine, and Polyglutamine Chains within the PRIME20 Model.

Understanding the conformational behavior of proteins has been a long-standing challenge to which computer simulations could contribute significantly. This concerns the folding behavior of proteins as well as the conformational statistics of intrinsically disordered proteins. A well-converged sampling of the conformational statistics over a broad range of control parameters is computationally extremely challenging and best addressed by coarse-grained modeling, for example, with an intermediate resolution model like the PRIME20 model. A comprehensive understanding of the thermodynamics and conformational statistics of individual protein chains is, however, not only a goal in itself but also a prerequisite for a better understanding of their aggregation tendency into oligomers and further into amyloid fibrils. We present here an extensive comparison of the ability of the PRIME20 model (in its documented variants in the literature) to faithfully reproduce the thermodynamics and statistics of three homopeptides having very different folding temperatures and different typical secondary structures.

The Conformational Ensemble of Polyglutamine-14 Chains: Specific Influences of Solubility Tail and Chromophores.

We address polyglutamine-14 in aqueous solution with specific chromophores and a solubility chain by means of a multiscale simulation approach, combining atomistic molecular dynamics simulations and coarse-grained Monte-Carlo conformational sampling. Despite the intrinsically disordered nature of the amyloidogenic polyglutamine, we observe transient characteristic structural motifs which exhibit a specific hydrogen bonding pattern. We illustrate the relationship between structure pattern and the distance distribution of a pair of chromophores attached to the peptide termini, in light of specific influence of a short solubility tail and the chromophores themselves on the conformational ensemble.

Wang-Landau simulation of Go model molecules.

Go-like models are one of the oldest protein modeling concepts in computational physics and have proven their value over and over for forty years. The essence of a Go model is to define a native contact matrix for a well-defined low-energy polymer configuration, e.g., the native state in the case of proteins or peptides. Many different potential shapes and many different cut-off distances in the definition of this native contact matrix have been proposed and applied. We investigate here the physical consequences of the choice for this cut-off distance in the Go models derived for a square-well tangent sphere homopolymer chain. For this purpose we are performing flat-histogram Monte Carlo simulations of Wang-Landau type, obtaining the thermodynamic and structural properties of such models over the complete temperature range. Differences and similarities with Go models for proteins and peptides are discussed.