相关论文: Best Practices for Alchemical Free Energy Calculat…
Calculating free energy differences is a topic of substantial interest and has many applications including molecular docking and hydration, solvation, and binding free energies which is used in computational drug discovery. However, in…
Free energies of molecules can be calculated by quantum computations or by normal mode classical calculations. However, the first can be computationally impractical for large molecules and the second is based on the assumption of harmonic…
The Alchemical Transfer Method (ATM) for the calculation of standard binding free energies of non-covalent molecular complexes is presented. The method is based on a coordinate displacement perturbation of the ligand between the receptor…
Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents,…
Free energy calculations are at the heart of physics-based analyses of biochemical processes. They allow us to quantify molecular recognition mechanisms, which determine a wide range of biological phenomena from how cells send and receive…
We propose a method to compute free-energy differences from nonadiabatic alchemical transformations using flow-based generative models. The method, nonadiabatic force matching, hinges on estimating the dissipation along an alchemical…
We devise automated workflows for the calculation of Helmholtz and Gibbs free energies and their temperature and pressure dependence and provide the corresponding computational tools. We employ non-equilibrium thermodynamics for evaluating…
Alchemical binding free energy (BFE) calculations offer an efficient and thermodynamically rigorous approach to in silico binding affinity predictions. As a result of decades of methodological improvements and recent advances in computer…
We study alchemical atomic energy partitioning as a method to estimate atomisation energies from atomic contributions which are defined in physically rigorous and general ways through use of the uniform electron gas as a joint reference. We…
We derive the optimal estimates of the free energies of an arbitrary number of thermodynamic states from nonequilibrium work measurements; the work data are collected from forward and reverse switching processes and obey a fluctuation…
We present an implementation of alchemical free energy simulations at the quantum mechanical level by directly interpolating the electronic Hamiltonian. The method is compatible with any level of electronic structure theory and requires…
The absolute free energy -- or partition function, equivalently -- of a molecule can be estimated computationally using a suitable reference system. Here, we demonstrate a practical method for staging such calculations by growing a molecule…
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…
One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is…
Accurately computing the free energies of biological processes is a cornerstone of computer-aided drug design but it is a daunting task. The need to sample vast conformational spaces and account for entropic contributions makes the…
A new simulated tempering method, which is referred to as simulated tempering umbrella sampling, for calculating the free energy of chemical reactions is proposed. First principles molecular dynamics simulations with this simulated…
From the onset of fundamental statistical mechanical constructs formulated in the late 19th century, alchemical free-energy methods slowly emerged and transitioned to become operational tools of biomolecular simulation applicable to a wide…
Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…
We present an extension of Alchemical Transfer Method (ATM) for the estimation of relative binding free energies of molecular complexes applicable to conventional as well as scaffold-hopping alchemical transformations. The method, named…
The accurate prediction of protein-ligand binding affinities is crucial for drug discovery. Alchemical free energy calculations have become a popular tool for this purpose. However, the accuracy and reliability of these methods can vary…