Equilibrium simulation of trp-cage in the presence of protein crowders

Abstract

Link to publication Citation for published version (APA): Bille, A., Linse, B., Mohanty, S., & Irbäck, A. (2015). Equilibrium simulation of trp-cage in the presence of protein crowders. Journal of Chemical Physics, 143(17), [175102]. DOI: 10.1063/1.4934997General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. While steric crowders tend to stabilize globular proteins, it has been found that protein crowders can have an either stabilizing or destabilizing effect, where a destabilization may arise from nonspecific attractive interactions between the test protein and the crowders. Here, we use Monte Carlo replicaexchange methods to explore the equilibrium behavior of the miniprotein trp-cage in the presence of protein crowders. Our results suggest that the surrounding crowders prevent trp-cage from adopting its global native fold, while giving rise to a stabilization of its main secondary-structure element, an α-helix. With the crowding agent used (bovine pancreatic trypsin inhibitor), the trp-cage-crowder interactions are found to be specific, involving a few key residues, most of which are prolines. The effects of these crowders are contrasted with those of hard-sphere crowders. C 2015 AIP Publishing LLC. Equilibrium simulation of trp-cage in the presence of protein crowders[http://dx

Markov modeling of peptide folding in the presence of protein crowders

“…[29][30][31][32][33][34] Recently, it was used by us to simulate the peptides trp-cage and GB1m3 in the presence of protein crowders. 8,26 Our simulations use the same fully atomistic representation of both the GB1m3 peptide and the crowder proteins. However, because of their high thermal stability, 24,25 the crowder proteins are modeled with a fixed backbone, and thus with side-chain rotations as their only internal degrees of freedom.…”

Protein folding/unfolding in the presence of interacting macromolecular crowders

“…In the study discussed in this section, we performed for the first time an atomic-level simulation study of the equilibrium folding thermodynamics of two peptides in the presence of explicit protein crowders [42,43]. The simulations require a minimal amount of input and yield a broad set of physical properties that, in principle, can be measured experimentally.…”

“…In our simulations, the part of GB1 most prone to form contacts with GB1m3 is indeed an edge strand (residues [42][43][44][45][46] belonging to the second β-hairpin (Fig. 4, right lower panel).…”

“…This section describes recent work by us based on Monte Carlo rather than molecular dynamics [42,43]. Using this approach, we investigated the equilibrium folding thermodynamics of two peptides in the presence of explicit protein crowders.…”

“…It begins in Section 2 with a brief overview of current approaches to this problem. Section 3 then describes recent work by us [42,43], where we used Monte Carlo methods, as implemented in our open-source software PROFASI [44], to simulate the folding thermodynamics of two structurally dissimilar peptides in the presence of explicit protein crowders.…”