Related papers: Free energy analyses of cell-penetrating peptides …
It is difficult to observe a spontaneous translocation of cell-penetrating peptides(CPPs) within a short time scale (e.g., a few hundred ns) in all-atom molecular dynamics(MD) simulations because the time required for the translocation of…
Finding and sampling multiple reaction channels for molecular transitions remains an important challenge in physical chemistry. Here we show that the weighted ensemble (WE) path sampling method can readily sample multiple channels. In a…
It has been known that the uptake mechanisms of cell-penetrating peptides(CPPs) depend on the experimental conditions such as concentration of peptides, lipid composition, temperature, etc. In this study we investigate the temperature…
Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating…
Understanding how different classes of molecules move across biological membranes is a prerequisite to predicting a solute's permeation rate, which is a critical factor in the fields of drug design and pharmacology. We use biased Molecular…
Weighted ensemble (WE) is an enhanced path-sampling method that is conceptually simple, widely applicable, and statistically exact. In a WE simulation, an ensemble of trajectories is periodically pruned or replicated to enhance sampling of…
Certain short polycations, such as TAT and oligoarginine, rapidly pass through the plasma membranes of mammalian cells by a mechanism called transduction, as well as by endocytosis and macropinocytosis. These cell-penetrating peptides…
The conformational free energy landscape of a system is a fundamental thermodynamic quantity of importance particularly in the study of soft matter and biological systems, in which the entropic contributions play a dominant role. While…
Cell-penetrating peptides (CPPs) such as HIV's trans-activating transcriptional activator (TAT) and polyarginine rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction. They may be medically…
Equilibrium formally can be represented as an ensemble of uncoupled systems undergoing unbiased dynamics in which detailed balance is maintained. Many non-equilibrium processes can be described by suitable subsets of the equilibrium…
Transition path sampling (TPS) is a powerful technique for investigating rare transitions, especially when the mechanism is unknown and one does not have access to the reaction coordinate. Straightforward application of TPS does not…
We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with multiple paths…
We introduce an extension to the Weighted Ensemble (WE) path sampling method to restrict sampling to a one dimensional path through a high dimensional phase space. Our method, which is based on the finite-temperature string method, permits…
Cell-penetrating peptides (CPPs) are powerful vectors for the intracellular delivery of a diverse array of therapeutic molecules. Despite their potential, the rational design of CPPs remains a challenging task that often requires extensive…
Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this…
The weighted ensemble (WE) simulation strategy provides unbiased sampling of non-equilibrium processes, such as molecular folding or binding, but the extraction of rate constants relies on characterizing steady state behavior.…
Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies…
We present a detailed comparison of computational efficiency and precision for several free energy difference ($\Delta F$) methods. The analysis includes both equilibrium and non-equilibrium approaches, and distinguishes between…
The conformation space of a 20-residue antiparallel $\beta$-sheet peptide, sampled by molecular dynamics simulations, is mapped to a network. Conformations are nodes of the network, and the transitions between them are links. The…
Quantum--Mechanical methods that are both computationally fast and accurate are not yet available for electronic excitations having charge transfer character. In this work, we present a significant step forward towards this goal for those…