2007/06/12 by Del Lucent, V. Vishal, Vijay S. Pande · 3 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Chemistry · #Protein Structure and Dynamics #Heat shock proteins research #Toxin Mechanisms and Immunotoxins #Protein folding #Downhill folding #Phi value analysis #Chaperonin #Solvent #Chemical physics #Folding (DSP implementation) #Chemistry #Contact order #Lattice protein #Biophysics #Folding funnel #Native state #Villin #Nanopore #Molten globule #Unfolded protein response #Crystallography #Nanotechnology #Materials science #Biochemistry #Actin #Biology
paper · pdf · doi:10.1073/pnas.0608256104
openalex publication_date 2007/06/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/24
Although most experimental and theoretical studies of protein folding involve proteins in vitro, the effects of spatial confinement may complicate protein folding in vivo. In this study, we examine the folding dynamics of villin (a small fast folding protein) with explicit solvent confined to an inert nanopore. We have calculated the probability of folding before unfolding (P(fold)) under various confinement regimes. Using P(fold) correlation techniques, we observed two competing effects. Confining protein alone promotes folding by destabilizing the unfolded state. In contrast, confining both protein and solvent gives rise to a solvent-mediated effect that destabilizes the native state. When both protein and solvent are confined we see unfolding to a compact unfolded state different from the unfolded state seen in bulk. Thus, we demonstrate that the confinement of solvent has a significant impact on protein kinetics and thermodynamics. We conclude with a discussion of the implications of these results for folding in confined environments such as the chaperonin cavity in vivo.