Effect of rate of chemical or thermal renaturation on refolding and aggregation of a simple lattice protein

Abstract

We used dynamic Monte Carlo simulation to investigate how changing the rate of chemical or thermal renaturation affects the folding and aggregation behavior of a system of simple, two-dimensional lattice protein molecules. Four renaturation methods were simulated: infinitely slow cooling; slow but finite cooling; quenching; and pulse renaturation. The infinitely slow cooling method, which is equivalent to dialysis or diafiltration, provides refolding yields that are relatively high and aggregates that are relatively small (mostly dimers or trimers). The slow but finite cooling method, which is equivalent to multiple-step dilution, provides refolding yields that are almost as high as those observed in the infinitely slow cooling case, but in a relatively short period of time. Quenching, which is equivalent to one-step dilution or quick quenching, is extremely slow and has low re- folding yields. A maximum appears in the refolding yield as a function of denaturant concentration in the simulation but disappears after a very long duration. Finally, the pulse renaturation method provides refolding yields that are substantially higher than those observed in the other three methods, even at high packing fractions. As in the early stages of quenching, there is a maximum in the refolding yield as a function of denaturant concentration when relatively large numbers of denatured chains are added to the refolding solution at each step.

Energy landscapes for adsorption of a protein-like HP chain as a function of native-state stability

“…HP chains have been studied extensively by Dill and co-workers [17,20] and many others (see, for instance, [21][22][23]) using Monte Carlo and molecular dynamics simulation techniques. Despite their obvious simplicity, the folding dynamics and solution thermodynamics of these model chains have significantly enriched our fundamental understanding of protein folding [20][21][22][23] and other macromolecular association events [24,25].…”

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

“…Given current computational capabilities, simpler models are required to simulate multiprotein systems. Computer simulations using low-resolution models, which are based on a coarse-grained representation of protein geometry and energetics, have been used by a few investigators to study protein aggregation [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] Although such models provide invaluable insights into the basic physics underlying protein aggregation in general, they do not adequately account for the different forces, such as hydrogen bonding, that play an important role in fibril formation.…”

Computational models of molecular self-organization in cellular environments

“…Such models have also proven useful for studies of protein aggregation [80,81] and, because of their long history in the protein-folding field [66,97,103] for studying the competition between protein folding and aggregation [29,35,69,99]. Lattice Monte Carlo models have also been used to study the influence of active transport phenomena and resulting heterogeneous reactant distributions on assembly kinetics.…”