Related papers: Force-dependent switch in protein unfolding pathwa…
A statistical mechanical description of flexible and semi-flexible polymer chains in a poor solvent is developed in the constant force and constant distance ensembles. We predict the existence of many intermediate states at low temperatures…
Mechanical unfolding trajectories, generated by applying constant force in optical tweezer experiments, show that RNA hairpins and the P5abc subdomain of the group I intron unfold reversibly. We use coarse-grained Go-like models for RNA…
Experimental observations suggest that proteins follow different pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the SH3 domain over a broad range of temperatures, and identify…
Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…
Theoretical studies of stretching proteins with slipknots reveal a surprising growth of their unfolding times when the stretching force crosses an intermediate threshold. This behavior arises as a consequence of the existence of alternative…
We have used kinetic Monte Carlo simulations to study the kinetics of unfolding of cross-linked polymer chains under mechanical loading. As the ends of a chain are pulled apart, the force transmitted by each crosslink increases until it…
Mechanically induced protein unfolding in the force-clamp apparatus is shown, in a coarse-grained model of ubiquitin, to have lognormal statistics above a treshold force and exponential below it. Correspondingly, the mean unfolding time is…
We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each…
We study theoretically the denaturation of single RNA molecules by mechanical stretching, focusing on signatures of the (un)folding pathway in molecular fluctuations. Our model describes the interactions between nucleotides by incorporating…
Biological forces govern essential cellular and molecular processes in all living organisms. Many cellular forces, e.g. those generated in cyclic conformational changes of biological machines, have repetitive components. However, little is…
Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…
The mechanical unfolding of an engineered protein composed of eight domains of Ig27 is investigated by using atomic force microscopy. Exploiting a fluctuation relation, the equilibrium free energy as a function of the molecule elongation is…
The energy landscapes of proteins have evolved to be different from most random heteropolymers. Many studies have concluded that evolutionary selection for rapid and reliable folding to a given structure that is stable at biological…
Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an…
A novel combination of discontinuous molecular dynamics and the Langevin equation, together with an intermediate-resolution model, are used to carry out long (several $\mu$s) simulation and study folding transition and transport of proteins…
The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…
The progress of the successive rounds of catalytic conversion of substrates into product(s) by a single enzyme is characterized by the distribution of turnover times. Establishing the most general form of dependence of this distribution on…
We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…
The folding of a peptide chain into a three dimensional structure is a thermodynamically driven process such that the chain naturally evolves to form domains of similar amino acids. The formation of this domain occurs by curling the one…
We establish a framework for assessing whether the transition state location of a biopolymer, which can be inferred from single molecule pulling experiments, corresponds to the ensemble of structures that have equal probability of reaching…