Dataset Information

Sampling of Organic Solutes in Aqueous and Heterogeneous Environments Using Oscillating Excess Chemical Potentials in Grand Canonical-like Monte Carlo-Molecular Dynamics Simulations.

ABSTRACT: Solute sampling of explicit bulk-phase aqueous environments in grand canonical (GC) ensemble simulations suffer from poor convergence due to low insertion probabilities of the solutes. To address this, we developed an iterative procedure involving Grand Canonical-like Monte Carlo (GCMC) and molecular dynamics (MD) simulations. Each iteration involves GCMC of both the solutes and water followed by MD, with the excess chemical potential (?ex) of both the solute and the water oscillated to attain their target concentrations in the simulation system. By periodically varying the ?ex of the water and solutes over the GCMC-MD iterations, solute exchange probabilities and the spatial distributions of the solutes improved. The utility of the oscillating-?ex GCMC-MD method is indicated by its ability to approximate the hydration free energy (HFE) of the individual solutes in aqueous solution as well as in dilute aqueous mixtures of multiple solutes. For seven organic solutes: benzene, propane, acetaldehyde, methanol, formamide, acetate, and methylammonium, the average ?ex of the solutes and the water converged close to their respective HFEs in both 1 M standard state and dilute aqueous mixture systems. The oscillating-?ex GCMC methodology is also able to drive solute sampling in proteins in aqueous environments as shown using the occluded binding pocket of the T4 lysozyme L99A mutant as a model system. The approach was shown to satisfactorily reproduce the free energy of binding of benzene as well as sample the functional group requirements of the occluded pocket consistent with the crystal structures of known ligands bound to the L99A mutant as well as their relative binding affinities.

SUBMITTER: Lakkaraju SK

PROVIDER: S-EPMC4053307 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sampling of Organic Solutes in Aqueous and Heterogeneous Environments Using Oscillating Excess Chemical Potentials in Grand Canonical-like Monte Carlo-Molecular Dynamics Simulations.

Lakkaraju Sirish Kaushik SK Raman E Prabhu EP Yu Wenbo W MacKerell Alexander D AD

Journal of chemical theory and computation 20140506 6

Solute sampling of explicit bulk-phase aqueous environments in grand canonical (GC) ensemble simulations suffer from poor convergence due to low insertion probabilities of the solutes. To address this, we developed an iterative procedure involving Grand Canonical-like Monte Carlo (GCMC) and molecular dynamics (MD) simulations. Each iteration involves GCMC of both the solutes and water followed by MD, with the excess chemical potential (μ<sub>ex</sub>) of both the solute and the water oscillated ...[more]

PMID: 24932136

Similar Datasets

Project description:Metal ions, particularly magnesium ions (Mg2+), play a role in stabilizing the tertiary structures of RNA molecules. Theoretical models and experimental techniques show that metal ions can change RNA dynamics and how it transitions through different stages of folding. However, the specific ways in which metal ions contribute to the formation and stabilization of RNA's tertiary structure are not fully understood at the atomic level. Here, we combined oscillating excess chemical potential Grand Canonical Monte Carlo (GCMC) and metadynamics to bias toward the sampling of unfolded states using reaction coordinates generated by machine learning allowing for examination of Mg2+-RNA interactions that contribute to stabilizing folded states of the pseudoknot found in the Twister ribozyme. GCMC is used to sample diverse ion distributions around the RNA with deep learning applied to iteratively generate system-specific reaction coordinates to maximize conformational sampling during metadynamics simulations. Results from 6 μs simulations performed on 9 individual systems indicate that Mg2+ ions play a crucial role in stabilizing the three-dimensional (3D) structure of the RNA by stabilizing specific interactions of phosphate groups or phosphate groups and bases of neighboring nucleotides. While many phosphates are accessible to interactions with Mg2+, it is observed that multiple, specific interactions are required to sample conformations close to the folded state; coordination of Mg2+ at individual specific sites facilitates sampling of folded conformations though unfolding ultimately occurs. It is only when multiple specific interactions occur, including the presence of specific inner-shell cation interactions linking two nucleotides, that conformations close to the folded state are stable. While many of the identified Mg2+ interactions are observed in the X-ray crystal structure of Twister, the present study suggests two new Mg2+ ion sites in the Twister ribozyme that contribute to stabilization. In addition, specific interactions with Mg2+ are observed that destabilize the local RNA structure, a process that may facilitate the folding of RNA into its correct structure.

Dataset Information

Sampling of Organic Solutes in Aqueous and Heterogeneous Environments Using Oscillating Excess Chemical Potentials in Grand Canonical-like Monte Carlo-Molecular Dynamics Simulations.

Publications

Sampling of Organic Solutes in Aqueous and Heterogeneous Environments Using Oscillating Excess Chemical Potentials in Grand Canonical-like Monte Carlo-Molecular Dynamics Simulations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets