Protein folding in high-dimensional spaces:hypergutters and the role of non-native interactions

The folding kinetics of a number of sequences for off-lattice continuum model of proteins is studied using Langevin simulations at two values of the friction coefficient. We show that there is a remarkable correlation between folding times, $\tau _{F}$, and $\sigma = (T_{\theta } - T_{F})/T_{\theta } $, where $T_{\theta }$ and $T_{F}$ are the equilibrium collapse and folding transition temperatures, respectively. The microscopic dynamics reveals several scenarios for the refo...

We assume that the protein folding process follows two autonomous steps: the conformational search for the native, mainly ruled by the hydrophobic effect; and, the final adjustment stage, which eventually gives stability to the native. Our main tool of investigation is a 3D lattice model provided with a ten-letter alphabet, the stereochemical model. This model was conceived for Monte Carlo (MC) simulations when one keeps in mind the kinetic behavior of protein-like chains in ...

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with the solvent, instantaneous power at each point within the molecule during folding, the fact that the process is stable in spite of myriad possible disturbances, potential stabilization of trajectory by chaos, and, of course, the exact physi...

How fast a post-translational nascent protein escapes from the ribosomal exit tunnel is relevant to its folding and protection against aggregation. Here, by using Langevin molecular dynamics, we show that non-local native interactions help decreasing the escape time, and foldable proteins generally escape much faster than same-length self-repulsive homopolymers at low temperatures. The escape process, however, is slowed down by the local interactions that stabilize the {\alph...

Energy landscape theory describes how a full-length protein can attain its native fold by sampling only a tiny fraction of all possible structures. Although protein folding is now understood to be concomitant with synthesis on the ribosome, there have been few attempts to modify energy landscape theory by accounting for cotranslational folding. Here we provide a model for cotranslational folding that leads to a natural definition of a nested energy landscape. By applying conc...

In this paper we investigate the role of native geometry on the kinetics of protein folding based on simple lattice models and Monte Carlo simulations. Results obtained within the scope of the Miyazawa-Jernigan indicate the existence of two dynamical folding regimes depending on the protein chain length. For chains larger than 80 amino acids the folding performance is sensitive to the native state's conformation. Smaller chains, with less than 80 amino acids, fold via two-sta...

We study folding dynamics of protein-like sequences on square lattice using physical move set that exhausts all possible conformational changes. By analytically solving the master equation, we follow the time-dependent probabilities of occupancy of all 802,075 conformations of 16-mers over 7-orders of time span. We find that (i) folding rates of these protein-like sequences of same length can differ by 4-orders of magnitude, (ii) folding rates of sequences of the same conform...

Proteins are minimally frustrated polymers. However, for realistic protein models non-native interactions must be taken into account. In this paper we analyze the effect of non-native interactions on the folding rate and on the folding free energy barrier. We present an analytic theory to account for the modification on the free energy landscape upon introduction of non-native contacts, added as a perturbation to the strong native interactions driving folding. Our theory pred...

We investigate the interplay between post-translational folding and escape of two small single-domain proteins at the ribosomal exit tunnel by using Langevin dynamics with coarse-grained models. It is shown that at temperatures lower or near the temperature of the fastest folding, folding proceeds concomitantly with the escape process, resulting in vectorial folding and enhancement of foldability of nascent proteins. The concomitance between the two processes, however, deteri...

We perform extensive Monte Carlo simulations of a lattice model and the Go potential to investigate the existence of folding pathways at the level of contact cluster formation for two native structures with markedly different geometries. Our analysis of folding pathways revealed a common underlying folding mechanism, based on nucleation phenomena, for both protein models. However, folding to the more complex geometry (i.e. that with more non-local contacts) is driven by a fol...