ArticleJournal of chemical theory and computation2023
ACES: Optimized Alchemically Enhanced Sampling.
Article in Journal of chemical theory and computation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Origins of Reactivity in SAM-Utilizing Ribozyme SAMURI-Catalyzed RNA Alkylation.Journal of the American Chemical Society · 2026Article
- Development and Test of Highly Accurate End Point Free Energy Methods. 4. Expanding Solvents Capability and logBB Prediction.The journal of physical chemistry. B · 2026Article
- Automated Force Field Developer and Optimizer Platform: Torsion Reparameterization.Journal of chemical information and modeling · 2026Article
- A Relative Binding Free Energy Framework for Structurally Dissimilar Molecules.Journal of chemical information and modeling · 2026Article
- SAMTI: Sampling Adaptive Thermodynamic Integration for Alchemical Free Energy Calculations.The journal of physical chemistry. B · 2025Article
- Template-Based Docking Using Automated Maximum Common Substructure Identification with EnzyDock: Mechanistic and Inhibitor Docking.Journal of chemical information and modeling · 2025Article
- Automated On-the-Fly Optimization of Resource Allocation for Efficient Free Energy Simulations.Journal of chemical information and modeling · 2025Article
- Aliphatic Polyester Recognition and Reactivity at the Active Cleft of a Fungal Cutinase.Journal of chemical information and modeling · 2025Article
- ABCG2: A Milestone Charge Model for Accurate Solvation Free Energy Calculation.Journal of chemical theory and computation · 2025Article
- Ligand Reorganization for End-Point Binding Free Energy Calculations: Identifying Preferred Poses of Fentanyls in the μ Opioid Receptor.Journal of chemical theory and computation · 2025Article
- Adaptive Lambda Scheduling: A Method for Computational Efficiency in Free Energy Perturbation Simulations.Journal of chemical information and modeling · 2025Article
- Multiple Topology Replica Exchange of Expanded Ensembles for Multidimensional Alchemical Calculations.Journal of chemical theory and computation · 2025Article
- Discovery of highly potent phosphodiesterase-1 inhibitors by a combined-structure free energy perturbation approach.Acta pharmaceutica Sinica. B · 2024Article
- Validating Small-Molecule Force Fields for Macrocyclic Compounds Using NMR Data in Different Solvents.Journal of chemical information and modeling · 2024Article
- The Role of General Acid Catalysis in the Mechanism of an Alkyl Transferase Ribozyme.ACS catalysis · 2024Article
- Improvements in Precision of Relative Binding Free Energy Calculations Afforded by the Alchemical Enhanced Sampling (ACES) Approach.Journal of chemical information and modeling · 2024Article
- Automated Adaptive Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2024Article
- Insights and Challenges in Correcting Force Field Based Solvation Free Energies Using a Neural Network Potential.The journal of physical chemistry. B · 2024Article
- Adsorption of Flavonoids in a Transcriptional Regulator TtgR: Relative Binding Free Energies and Intermolecular Interactions.The journal of physical chemistry. B · 2024Article
- Computational Investigation of BMAA and Its Carbamate Adducts as Potential GluR2 Modulators.Journal of chemical information and modeling · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We present an alchemical enhanced sampling (ACES) method implemented in the GPU-accelerated AMBER free energy MD engine. The methods hinges on the creation of an "enhanced sampling state" by reducing or eliminating selected potential energy terms and interactions that lead to kinetic traps and conformational barriers while maintaining those terms that curtail the need to otherwise sample large volumes of phase space. For example, the enhanced sampling state might involve transforming regions of a ligand and/or protein side chain into a noninteracting "dummy state" with internal electrostatics and torsion angle terms turned off. The enhanced sampling state is connected to a real-state end point through a Hamiltonian replica exchange (HREMD) framework that is facilitated by newly developed alchemical transformation pathways and smoothstep softcore potentials. This creates a counterdiffusion of real and enhanced-sampling states along the HREMD network. The effect of a differential response of the environment to the real and enhanced-sampling states is minimized by leveraging the dual topology framework in AMBER to construct a counterbalancing HREMD network in the opposite alchemical direction with the same (or similar) real and enhanced sampling states at inverted end points. The method has been demonstrated in a series of test cases of increasing complexity where traditional MD, and in several cases alternative REST2-like enhanced sampling methods, are shown to fail. The hydration free energy for acetic acid was shown to be independent of the starting conformation, and the values for four additional edge case molecules from the FreeSolv database were shown to have a significantly closer agreement with experiment using ACES. The method was further able to handle different rotamer states in a Cdk2 ligand identified as fractionally occupied in crystal structures. Finally, ACES was applied to T4-lysozyme and demonstrated that the side chain distribution of V111χ
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.