Related papers: Best Practices for Alchemical Free Energy Calculat…
Recent advances in non-equilibrium statistical mechanics and single molecule technologies make it possible to extract free energy differences from irreversible work measurements in pulling experiments. To date, free energy recovery has been…
Thermodynamic integration (TI) offers a rigorous method for estimating free-energy differences by integrating over a sequence of interpolating conformational ensembles. However, TI calculations are computationally expensive and typically…
"Alchemical" interpolation paths, i.e.~coupling systems along fictitious paths that without realistic correspondence, are frequently used within materials and molecular modeling and simulation protocols for the estimation of relative…
This report details an approach to improve the accuracy and precision of free energy difference estimates using thermodynamic integration data (slope of the free energy with respect to the switching variable lambda) and its application to…
We report the results of our participation in the SAMPL8 GDCC Blind Challenge for host-guest binding affinity predictions. Absolute binding affinity prediction is of central importance to the biophysics of molecular association and…
We present a methodology for accelerating the estimation of the free energy from path integral Monte Carlo simulations by considering an intermediate artificial reference system where interactions are inexpensive to evaluate numerically.…
An expression is derived for the classical free energy difference between two configurations of a system, in terms of an ensemble of finite-time measurements of the work performed in parametrically switching from one configuration to the…
Free energies play a central role in many descriptions of equilibrium and non-equilibrium properties of solids. Continuum partial differential equations (PDEs) of atomic transport, phase transformations and mechanics often rely on first and…
Atomistic simulations are employed to demonstrate the existence of a well-defined thermodynamic phase transformation between grain boundary (GB) phases with different atomic structures. The free energy of different interface structures for…
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…
With the help of metadynamics it is possible to calculate efficiently the free energy of systems displaying high energy barriers as a function of few selected "collective variables". In doing this, the contribution of all the other degrees…
Accurate calculation of free energies and their derivatives is central to assessing the thermodynamic stability of molecular and particulate systems across length scales. Yet such quantities can be difficult to compute reliably in strongly…
According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the ligand apo ensemble and a rigid…
We present a new method to compute free energies at a quantum mechanical (QM) level of theory from molecular simulations using cheap reference potential energy functions, such as force fields. To overcome the poor overlap between the…
Recent theoretical predictions and experimental measurements have demonstrated that equilibrium free energy differences can be obtained from exponential averages of nonequilibrium work values. These results are similar in structure, but not…
Motor enzymes catalyze chemical reactions, like the hydrolysis of ATP, and in the process they also perform work. Recent studies indicate that motor enzymes perform work with specific intermediate steps in their catalyzed reactions,…
Predicting the physico-chemical properties of pure substances and mixtures is a central task in thermodynamics. Established prediction methods range from fully physics-based ab-initio calculations, which are only feasible for very simple…
The Jarzynski equality allows the calculation of free-energy differences using values of work measured from nonequilibrium trajectories. The number of trajectories required to accurately estimate free-energy differences in this way grows…
We present receptor hopping and receptor swapping free energy estimation protocols based on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands to two arbitrary receptors. The receptor hopping protocol,…
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…