ArticleMolecules (Basel, Switzerland)2022
Does Hamiltonian Replica Exchange via Lambda-Hopping Enhance the Sampling in Alchemical Free Energy Calculations?
Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Multiple Topology Replica Exchange of Expanded Ensembles for Multidimensional Alchemical Calculations.Journal of chemical theory and computation · 2025Article
- Dealing with Induced Fit, Conformational Selection, and Secondary Poses in Molecular Dynamics Simulations for Reliable Free Energy Predictions.Journal of chemical theory and computation · 2023Article
- Comparison of Equilibrium and Nonequilibrium Approaches for Relative Binding Free Energy Predictions.Journal of chemical theory and computation · 2023Article
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Abstract
In the context of computational drug design, we examine the effectiveness of the enhanced sampling techniques in state-of-the-art free energy calculations based on alchemical molecular dynamics simulations. In a paradigmatic molecule with competition between conformationally restrained E and Z isomers whose probability ratio is strongly affected by the coupling with the environment, we compare the so-called λ-hopping technique to the Hamiltonian replica exchange methods assessing their convergence behavior as a function of the enhanced sampling protocols (number of replicas, scaling factors, simulation times). We found that the pure λ-hopping, commonly used in solvation and binding free energy calculations via alchemical free energy perturbation techniques, is ineffective in enhancing the sampling of the isomeric states, exhibiting a pathological dependence on the initial conditions. Correct sampling can be restored in λ-hopping simulation by the addition of a "hot-zone" scaling factor to the λ-stratification (FEP
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