Related papers: Structural transition states explored with minimal…
Despite the significant increase in computational power, molecular modeling of protein structure using classical all-atom approaches remains inefficient, at least for most of the protein targets in the focus of biomedical research. Perhaps…
A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…
We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a…
Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small fast folding proteins. To investigate the extent of the…
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…
A molecular understanding of how protein function is related to protein structure will require an ability to understand large conformational changes between multiple states. Unfortunately these states are often separated by high free energy…
We present a new method that enables the identification and analysis of both transition and metastable conformational states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented and studied by…
All-atom and coarse-grained molecular dynamics are two widely used computational tools to study the conformational states of proteins. Yet, these two simulation methods suffer from the fact that without access to supercomputing resources,…
Protein folding processes are generally described statistically with the help of multidimensional free energy landscape, typically reduced to a 1-D free energy profile along good reaction co-ordinate. There are many physical parameters…
We explore how inherent flexibility of a protein molecule influences the mechanism controlling the kinetics of allosteric transitions using a variational model inspired from work in protein folding. The striking differences in the predicted…
This study reveals the essence of ligand recognition mechanisms by which calmodulin (CaM) controls a variety of Ca2+ signaling processes. We study eight forms of calcium-loaded CaM each with distinct conformational states. Reducing the…
Interactions between a protein and a ligand are often accompanied by a redistribution of the population of thermally accessible conformations. This dynamic response of the protein's functional energy landscape enables a protein to modulate…
It is important to extract reaction coordinates or order parameters from protein simulations in order to investigate the local minimum-energy states and the transitions between them. The most popular method to obtain such data is principal…
We introduce a variational approximation to the microscopic dynamics of rare conformational transitions of macromolecules. Within this framework it is possible to simulate on a small computer cluster reactions as complex as protein folding,…
A simple way to get insights about the possible functional motions of a protein is to perform a normal mode analysis (NMA). Indeed, it has been shown that low-frequency modes thus obtained are often closely related to domain motions…
Self-organized pattern formation is vital for many biological processes. Reaction-diffusion models have advanced our understanding of how biological systems develop spatial structures, starting from homogeneity. However, biological…
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…
Understanding the protein folding process is an outstanding issue in biophysics; recent developments in molecular dynamics simulation have provided insights into this phenomenon. However, the large freedom of atomic motion hinders the…
A steadily growing computational power is employed to perform molecular dynamics simulations of biological macromolecules, which represents at the same time an immense opportunity and a formidable challenge. In fact, large amounts of data…
Chromatin and associated proteins constitute the highly folded structure of chromosomes. We consider a self-avoiding polymer model of the chromatin, segments of which may get cross-linked via protein binders that repel each other. The…