相关论文: Binding Selectivity Analysis from Alchemical Recep…

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…

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 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…

The Alchemical Transfer Method (ATM) is herein validated against the relative binding free energies of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and the AToM-OpenMM software…

We present the Alchemical Transfer with Coordinate Swapping (ATS) method to enable the calculation of the relative binding free energies between large congeneric ligands and single-point mutant peptides to protein receptors with the…

We present a new method that combines alchemical transformation with physical pathway to accurately and efficiently compute the absolute binding free energy of receptor-ligand complex. Currently, the double decoupling method (DDM) and the…

We present an analytical description of the Alchemical Transfer Method (ATM) for molecular binding using the Potential Distribution Theory (PDT) formalism. ATM models the binding free energy by mapping the bound and unbound states of the…

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…

A rigorous formalism for estimating noncovalent binding free energies and thermodynamic expectations from calculations in which receptor configurations are sampled independently from the ligand is derived. Due to this separation, receptor…

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…

The primary limitation for the application of alchemical free energy methods to a wider variety of complex molecular systems is achieving reasonable sampling. Flexible binding complexes often have high free energy barriers, which require…

In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non covalent bonding in drug receptor systems. I show that most of the pitfalls and entanglements for the…

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 apply the Alchemical Transfer Method (ATM) and a bespoke fixed partial charge force field to the SAMPL9 bCD host-guest binding free energy prediction challenge that comprises a combination of complexes formed between five phenothiazine…

This letter gives results on improving protein-ligand binding affinity predictions based on molecular dynamics simulations using machine learning potentials with a hybrid neural network potential and molecular mechanics methodology…

We introduce an efficient and robust method to compute alchemical free energy differences, resulting from the application of multiple walker Adaptive Biasing Force (ABF) in conjunction with strongly damped Langevin $\lambda$-dynamics.…

The theory of receptor-ligand binding equilibria has long been well-established in biochemistry, and was primarily constructed to describe dilute aqueous solutions. Accordingly, few computational approaches have been developed for making…

Absolute Binding Free Energy (ABFE) methods are among the most accurate computational techniques for predicting protein-ligand binding affinities, but their utility is limited by the need for many simulations of alchemically modified…

Alchemical Grid Dock (AlGDock) is open-source software designed to compute the binding potential of mean force (BPMF) - the binding free energy between a flexible ligand and a rigid receptor - for a small organic ligand and a biological…

Prediction of protein-ligand binding affinity is a major goal in drug discovery. Generally, free energy gap is calculated between two states (e.g., ligand binding and unbinding). The energy gap implicitly includes the effects of changes in…