ArticleJournal of chemical theory and computation2019
Use of Interaction Energies in QM/MM Free Energy Simulations.
Article in Journal of chemical theory and computation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- What to Make of Zero: Resolving the Statistical Noise from Conformational Reorganization in Alchemical Binding Free Energy Estimates with Metadynamics Sampling.Journal of chemical theory and computation · 2024Article
- Accurate and Efficient Multilevel Free Energy Simulations with Neural Network-Assisted Enhanced Sampling.Journal of chemical theory and computation · 2023Article
- Exploring Routes to Enhance the Calculation of Free Energy Differences via Non-Equilibrium Work SQM/MM Switching Simulations Using Hybrid Charge Intermediates between MM and SQM Levels of Theory or Non-Linear Switching Schemes.Molecules (Basel, Switzerland) · 2023Article
- Factors That Determine the Variation of Equilibrium and Kinetic Properties of QM/MM Enzyme Simulations: QM Region, Conformation, and Boundary Condition.Journal of chemical theory and computation · 2022Article
- AffordableThe journal of physical chemistry. A · 2021Article
- Performing Molecular Dynamics Simulations and Computing Hydration Free Energies on the B3LYP-D3(BJ) Potential Energy Surface with Adaptive Force Matching: A Benchmark Study with Seven Alcohols and One Amine.ACS physical chemistry Au · 2021Article
- Exploring the Minimum-Energy Pathways and Free-Energy Profiles of Enzymatic Reactions with QM/MM Calculations.The journal of physical chemistry. B · 2021Article
- Accelerated Computation of Free Energy Profile atJournal of chemical theory and computation · 2021Article
- Biomolecular QM/MM Simulations: What Are Some of the "Burning Issues"?The journal of physical chemistry. B · 2021Article
- On the faithfulness of molecular mechanics representations of proteins towards quantum-mechanical energy surfaces.Interface focus · 2020Article
- Accelerated Computation of Free Energy Profile atJournal of chemical theory and computation · 2020Article
- Multi-level free energy simulation with a staged transformation approach.The Journal of chemical physics · 2020Article
- Development of a Robust Indirect Approach for MM → QM Free Energy Calculations That Combines Force-Matched Reference Potential and Bennett's Acceptance Ratio Methods.Journal of chemical theory and computation · 2019Article
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Authors and funding
3 authors.
Funding
Abstract
The use of the most accurate (i.e., QM or QM/MM) levels of theory for free energy simulations (FES) is typically not possible. Primarily, this is because the computational cost associated with the extensive configurational sampling needed for converging FES is prohibitive. To ensure the feasibility of QM-based FES, the "indirect" approach is generally taken, necessitating a free energy calculation between the MM and QM/MM potential energy surfaces. Ideally, this step is performed with standard free energy perturbation (Zwanzig's equation) as it only requires simulations be carried out at the low level of theory; however, work from several groups over the past few years has conclusively shown that Zwanzig's equation is ill-suited to this task. As such, many approximations have arisen to mitigate difficulties with Zwanzig's equation. One particularly popular notion is that the convergence of Zwanzig's equation can be improved by using interaction energy differences instead of total energy differences. Although problematic numerical fluctuations (a major problem when using Zwanzig's equation) are indeed reduced, our results and analysis demonstrate that this "interaction energy approximation" (IEA) is theoretically incorrect, and the implicit approximation invoked is spurious at best. Herein, we demonstrate this via solvation free energy calculations using IEA from two different low levels of theory to the same target high level. Results from this proof-of-concept consistently yield the wrong results, deviating by ∼1.5 kcal/mol from the rigorously obtained value.
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