Modern alchemical free energy methods for drug discovery explained

DM York - ACS Physical Chemistry Au, 2023 - ACS Publications
This Perspective provides a contextual explanation of the current state-of-the-art alchemical
free energy methods and their role in drug discovery as well as highlights select emerging …

An overview of the SAMPL8 host–guest binding challenge

M Amezcua, J Setiadi, Y Ge, DL Mobley - Journal of computer-aided …, 2022 - Springer
The SAMPL series of challenges aim to focus the community on specific modeling
challenges, while testing and hopefully driving progress of computational methods to help …

Performance and Analysis of the Alchemical Transfer Method for Binding-Free-Energy Predictions of Diverse Ligands

L Chen, Y Wu, C Wu, A Silveira… - Journal of Chemical …, 2023 - ACS Publications
The Alchemical Transfer Method (ATM) is herein validated against the relative binding-free
energies (RBFEs) of a diverse set of protein–ligand complexes. We employed a streamlined …

Alchemical Enhanced Sampling with Optimized Phase Space Overlap

S Zhang, TJ Giese, TS Lee… - Journal of Chemical Theory …, 2024 - ACS Publications
An alchemical enhanced sampling (ACES) method has recently been introduced to facilitate
importance sampling in free energy simulations. The method achieves enhanced sampling …

Taming multiple binding poses in alchemical binding free energy prediction: the β-cyclodextrin host–guest SAMPL9 blinded challenge

S Khuttan, S Azimi, JZ Wu, S Dick, C Wu… - Physical Chemistry …, 2023 - pubs.rsc.org
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 …

The SAMPL9 host-guest blind challenge: an overview of binding free energy predictive accuracy

M Amezcua, J Setiadi, DL Mobley - Physical Chemistry Chemical …, 2024 - pubs.rsc.org
We report the results of the SAMPL9 host–guest blind challenge for predicting binding free
energies. The challenge focused on macrocycles from pillar [n]-arene and cyclodextrin host …

Developing end-point methods for absolute binding free energy calculation using the Boltzmann-quasiharmonic model

L Wickstrom, E Gallicchio, L Chen… - Physical Chemistry …, 2022 - pubs.rsc.org
Understanding the physical forces underlying receptor–ligand binding requires robust
methods for analyzing the binding thermodynamics. In end-point binding free energy …

Expanded ensemble predictions of absolute binding free energies in the SAMPL9 host–guest challenge

MFD Hurley, RM Raddi, JG Pattis… - Physical Chemistry …, 2023 - pubs.rsc.org
As part of the SAMPL9 community-wide blind host–guest challenge, we implemented an
expanded ensemble workflow to predict absolute binding free energies for 13 small …

Binding Selectivity Analysis from Alchemical Receptor Hopping and Ligand Swapping Free Energy Calculations

S Azimi, E Gallicchio - arXiv preprint arXiv:2402.06887, 2024 - arxiv.org
We present receptor-hopping and ligand-swapping free energy estimation protocols based
on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands …

Potential Distribution Theory of Alchemical Transfer

S Azimi, E Gallicchio - arXiv preprint arXiv:2407.14713, 2024 - arxiv.org
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 …