Related papers: Force-dependent switch in protein unfolding pathwa…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
Living systems rely on coordinated molecular interactions, especially those related to gene expression and protein activity. The Unfolded Protein Response is a crucial mechanism in eukaryotic cells, activated when unfolded proteins exceed a…
Using force as a probe to map the folding landscapes of RNA molecules has become a reality thanks to major advances in single molecule pulling experiments. Although the unfolding pathways under tension are complicated to predict studies in…
Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to…
Force-clamp spectroscopy reveals the unfolding and disulfide bond rupture times of single protein molecules as a function of the stretching force, point mutations and solvent conditions. The statistics of these times reveal whether the…
DNA hairpin molecules with periodic base sequences can be expected to exhibit a regular coarse-grained free energy landscape (FEL) as function of the number of open base pairs and applied mechanical force. Using a commonly employed model,…
We present a theoretical study of single-stranded DNA under stretching. Within the proposed framework, the effects of basepairing on the mechanical response of the molecule can be studied in combination with an arbitrary underlying model of…
Growing experimental evidence shows that proteins follow one or a few distinct paths when folding. We propose in this paper a procedure to parametrize these observed pathways, and from this parametrization construct effective Hamiltonians…
We investigate the mechanical unfolding of the tenth type III domain from fibronectin, FnIII10, both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and…
We employ simulations of model proteins to study folding on rugged energy landscapes. We construct ``first-passage'' networks as the system transitions from unfolded to native states. The nodes and bonds in these networks correspond to…
Proteins with multiple binding sites play important roles in cell signaling systems by nucleating protein complexes in which, for example, enzymes and substrates are co-localized. Proteins that specialize in this function are called by a…
Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes, using laser optical tweezer (LOT) experiments have begun to reveal the features of the energy landscape that cannot be easily explored using conventional…
The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…
The prediction of protein stability changes following single-point mutations plays a pivotal role in computational biology, particularly in areas like drug discovery, enzyme reengineering, and genetic disease analysis. Although…
Drug resistance to HIV-1 Protease involves accumulation of multiple mutations in the protein. Here we investigate the role of these mutations by using molecular dynamics simulations which exploit the influence of the native-state topology…
We use mesoscopic non-equilibrium thermodynamics theory to describe RNA unfolding under tension. The theory introduces reaction coordinates, characterizing a continuum of states for each bond in the molecule. The unfolding considered is so…
We provide evidence that the energy landscapes of folded proteins do not shift with temperature, but the onset of functional dynamics is associated with its effective sampling. The motion of the backbone is described by three distinct…
Time-resolved single-molecule biophysical experiments yield data that contain a wealth of dynamic information, in addition to the equilibrium distributions derived from histograms of the time series. In typical force spectroscopic setups…
We introduce a method for calculating the extent to which chain non-crossing is important in the most efficient, optimal trajectories or pathways for a protein to fold. This involves recording all unphysical crossing events of a ghost…
Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness…