相关论文: Using binding free energy to guide ligand design

Accurate prediction of protein-ligand binding affinities is crucial in drug discovery, particularly during hit-to-lead and lead optimization phases, however, limitations in ligand force fields continue to impact prediction accuracy. In this…

Simulation studies are used to evaluate and compare the properties of statistical methods in controlled experimental settings. In most cases, performing a simulation study requires knowledge of the true value of the parameter, or estimand,…

Resistance to chemotherapy and molecularly targeted therapies is a major factor in limiting the effectiveness of cancer treatment. In many cases, resistance can be linked to genetic changes in target proteins, either pre-existing or…

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…

Proteins change their charge state through protonation and redox reactions as well as through binding charged ligands. The free energy of these reactions are dominated by solvation and electrostatic energies and modulated by protein…

Using the specific model of a system of like charged ions confined between two planar like charged surfaces, we compare the predictions for the energy and density profile of four simulation methods available to treat the long range Coulomb…

We propose an adiabatic reweighting algorithm for computing the free energy along an external parameter from adaptive molecular dynamics simulations. The adaptive bias is estimated using Bayes identity and information from all the sampled…

We analyze a new Monte Carlo method which uses transition matrix in the space of energy. This method gives an efficient reweighting technique. The associated artificial dynamics is a constrained random walk in energy, producing the result…

Estimating the free energy in molecular simulation requires, implicitly or explicitly, counting how many times the system is observed in a finite region. If the simulation is biased by an external potential, the weight of the configurations…

Binding energies calculated from using the Bethe-Salpeter equation in the simplest ladder approximation significantly differ from those obtained in the non-relativistic standard instantaneous approximation. While they should a priori be…

I present a cluster Monte Carlo algorithm that gives direct access to the interface free energy of Ising models. The basic idea is to simulate an ensemble that consists of both configurations with periodic and with antiperiodic boundary…

We present an approximate method for calculating the electrostatic free energy of concentrated protein solutions. Our method uses a cell model and accounts for both the coulomb energy and the entropic cost of Donnan salt partitioning. The…

Recently, nanofluidics experiments have been used to characterize the behavior of single DNA molecules confined to narrow slits etched with arrays of nanopits. Analysis of the experimental data relies on analytical estimates of the…

Optimal structure of proteins is described by linear stochastic differential equation with mean decrease of free energy and volatility. Structure determining strategy is given by a twin of stochastic variables for which empirical conditions…

Monte Carlo evaluation is used to calculate heavy-ion elastic scattering including the center-of-mass correction and the Coulomb interaction.Angular distributions are presented for a number of nuclear pairs over a wide energy range using…

We study the thermodynamics and kinetics of folding for a small peptide. Our data rely on Monte Carlo simulations where the interactions among all atoms are taken into account. Monte Carlo kinetics is used to study folding of the peptide at…

The quantitative description of model protein folding kinetics using a diffusive collective reaction coordinate is examined. Direct folding kinetics, diffusional coefficients and free energy profiles are determined from Monte Carlo…

The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co--evolving proteins by means of an inverse…

Predictions of relative stabilities of (competing) molecular crystals are of great technological relevance, most notably for the pharmaceutical industry. However, they present a long-standing challenge for modeling, as often minuscule free…

We present a method for determining the free energy dependence on a selected number of collective variables using an adaptive bias. The formalism provides a unified description which has metadynamics and canonical sampling as limiting…