Related papers: Elusive Unfoldability: Learning a Contact Potentia…
Exploring and understanding the protein-folding problem has been a long-standing challenge in molecular biology. Here, using molecular dynamics simulation, we reveal how parallel distributed adjacent planar peptide groups of unfolded…
A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven different helix bundle proteins. The protocol, which includes…
A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…
What energetic and solvation effects underlie the remarkable two-state thermodynamics and folding/unfolding kinetics of small single-domain proteins? To address this question, we investigate the folding and unfolding of a hierarchy of…
A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The…
An optimization technique is used to determine the pairwise interactions between amino acids in globular proteins. A numerical strategy is applied to a set of proteins for maximizing the native fold stability with respect to alternative…
Knowledge-based potentials were developed to investigate the differentiation of native structures from their decoy sets. This work presents the construction of two different distance-dependent potential energy functions based on two…
Simple two-state folding kinetics of many small single-domain proteins are characterized by chevron plots with linear folding and unfolding arms consistent with a two-state description of equilibrium thermodynamics. This phenomenon is…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
Natively unfolded proteins exist as an ensemble of flexible conformations lacking a well defined tertiary structure along a large portion of their polypeptide chain. Despite the absence of a stable configuration, they are involved in…
The potential energy surface of an off-lattice model protein is characterized in detail by constructing a disconnectivity graph and by examining the organisation of pathways on the surface. The results clearly reveal the frustration…
Despite many advances in computational modeling of protein structures, these methods have not been widely utilized by experimental structural biologists. Two major obstacles are preventing the transition from a purely-experimental to a…
The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling…
Protein folding is one of the age-old biological problems that refers to the mechanism of understanding and predicting how a protein's linear sequence of amino acids folds into its specific three dimensional structure.This structure is…
Understanding the principles of protein folding is a cornerstone of computational biology, with implications for drug design, bioengineering, and the understanding of fundamental biological processes. Lattice protein folding models offer a…
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…
Proteins fold to a specific functional conformation with a densely packed hydrophobic core that controls their stability. We develop a geometric, yet all-atom model for proteins that explains the universal core packing fraction of…
We present a new method to extract distance and orientation dependent potentials between amino acid side chains using a database of protein structures and the standard Boltzmann device. The importance of orientation dependent interactions…
We propose a novel method for the determination of the effective interaction potential between the amino acids of a protein. The strategy is based on the combination of a new optimization procedure and a geometrical argument, which also…
Natural proteins fold to a unique, thermodynamically dominant state. Modeling of the folding process and prediction of the native fold of proteins are two major unsolved problems in biophysics. Here, we show successful all-atom ab initio…