Related papers: Conformational Entropy as Collective Variable for …
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…
Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…
The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated…
Configurational entropy is an important factor in the free energy change of many macromolecular recognition and binding processes, and has been intensively studied. Despite great progresses that have been made, the global sampling remains…
Designing an appropriate set of collective variables is crucial to the success of several enhanced sampling methods. Here we focus on how to obtain such variables from information limited to the metastable states. We characterize these…
Enhanced sampling methods typically require predefined collective variables (CVs) that presuppose knowledge of reaction coordinates, restricting the discovery of unanticipated transition mechanisms or intermediates. Here, we show that a…
We review a selection of methods for performing enhanced sampling in molecular dynamics simulations. We consider methods based on collective variable biasing and on tempering, and offer both historical and contemporary perspectives. In…
We solve a model that takes into account entropic barriers, frustration, and the organization of a protein-like molecule. For a chain of size $M$, there is an effective folding transition to an ordered structure. Without frustration, this…
Enhanced sampling techniques such as umbrella sampling and metadynamics are now routinely used to provide information on how the thermodynamic potential, or free energy, depends on a small number of collective variables. The free energy…
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…
Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…
In modern day simulations of many-body systems much of the computational complexity is shifted to the identification of slowly changing molecular order parameters called collective variables (CV) or reaction coordinates. A vast array of…
An information theory model is used to construct a molecular explanation why hydrophobic solvation entropies measured in calorimetry of protein unfolding converge at a common temperature. The entropy convergence follows from the weak…
We construct a Hamiltonian for a single domain protein where the contact enthalpy and the chain entropy decrease linearly with the number of native contacts. The hydration effect upon protein unfolding is included by modeling water as ideal…
In this paper we combine two powerful computational techniques, well-tempered metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy…
Methods that combine collective variable (CV) based enhanced sampling and global tempering approaches are used in speeding-up the conformational sampling and free energy calculation of large and soft systems with a plethora of energy…
Many processes of scientific importance are characterized by time scales that extend far beyond the reach of standard simulation techniques. To circumvent this impediment a plethora of enhanced sampling methods has been developed. One…
We refine a protein model that reproduces fundamental aspects of protein thermodynamics. The model exhibits two transitions, hot and cold unfolding. The number of relevant parameters is reduced to three: 1) binding energy of folding…
Understanding protein conformational dynamics is essential for elucidating biological function but remains challenging due to the wide range of timescales and the complexity of collective motions. Enhanced sampling methods overcome…
Entropy and free-energy estimation are key in thermodynamic characterization of simulated systems ranging from spin models through polymers, colloids, protein structure, and drug-design. Current techniques suffer from being model specific,…