Proteins appear to fold by diverse pathways, but variations of a simple mechanism - nucleation-condensation - describe the overall features of folding of most domains. In general, secondary structure is inherently unstable and its stability is enhanced by tertiary interactions. Consequently, an extensive interplay of secondary and tertiary interactions determines the transition-state for foldin...

In vivo, many proteases are synthesized as larger precursors. During the maturation process, the catalytically active protease domain is released from the larger polypeptide or pro-enzyme by one or more proteolytic processing steps. In several well studied cases, amino-terminal pro regions have been shown to play a fundamental role in the folding of the associated protease domains. The mechanis...

Molecular Dynamics-based simulations have been employed to study the protein folding process, in which a protein acquires its functional three-dimensional structure. This has resulted in a large number of protein folding trajectories. As a result, it becomes increasingly important to analyze such data to facilitate a deeper understanding of the protein folding mechanism. In this paper, we focus...

pH jumps are a truly biomimetic technique to initiate non-equilibrium dynamics of biomolecules. In this work, the pH jump induced alpha-helix folding of poly-L-glutamic acid is investigated upon proton release from o-nitrobenzaldehyde. The aim of this work is twofold: On the one hand, design criteria of pH jump experiments are discussed, on the other hand, the folding mechanism of poly-L-glutam...

A unified and coherent picture for the mechanism of protein folding is emerging. The crucial factor in folding is the cooperativity of multiple interactions that is required for stability of the folded state.

Understanding the mechanism of protein secondary structure formation is an essential part of the protein-folding puzzle. Here we describe a simple model for the formation of a beta hairpin, motivated by the fact that folding of a beta hairpin captures much of the basic physics of protein folding. The modeled hairpin is composed of two interacting Gaussian chains with one pairwise (two-body) and...

The elongated three-helix bundle domains spectrin R16 and R17 fold some two to three orders of magnitude more slowly than their homologue R15. We have shown that this slow folding is due, at least in part, to roughness in the free-energy landscape of R16 and R17. We have proposed that this roughness is due to a frustrated search for the correct docking of partly preformed helices. However, this...

Repeat proteins are widespread in nature, with many of them functioning as binding molecules in protein-protein recognition. Their simple structural architecture is used in biotechnology for generating proteins with high affinities to target proteins. Recent folding studies of ankyrin repeat (AR) proteins revealed a new mechanism of protein folding. The formation of an intermediate state is rat...

The mechanism and thermodynamics of folding of the Src homology 3 (SH3) protein domain are characterized at an atomic level through molecular dynamics with importance sampling. This methodology enables the construction of the folding free energy landscape of the protein as a function of representative reaction coordinates. We observe that folding proceeds in a downhill manner under native condi...