• Media type: E-Article
  • Title: How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case
  • Contributor: Paissoni, Cristina; Camilloni, Carlo
  • Published: Frontiers Media SA, 2021
  • Published in: Frontiers in Molecular Biosciences, 8 (2021)
  • Language: Not determined
  • DOI: 10.3389/fmolb.2021.694130
  • ISSN: 2296-889X
  • Origination:
  • Footnote:
  • Description: The reliability and usefulness of molecular dynamics simulations of equilibrium processes rests on their statistical precision and their capability to generate conformational ensembles in agreement with available experimental knowledge. Metadynamics Metainference (M&M), coupling molecular dynamics with the enhanced sampling ability of Metadynamics and with the ability to integrate experimental information of Metainference, can in principle achieve both goals. Here we show that three different Metadynamics setups provide converged estimate of the populations of the three-states populated by a model peptide. Errors are estimated correctly by block averaging, but higher precision is obtained by performing independent replicates. One effect of Metadynamics is that of dramatically decreasing the number of effective frames resulting from the simulations and this is relevant for M&M where the number of replicas should be large enough to capture the conformational heterogeneity behind the experimental data. Our simulations allow also us to propose that monitoring the relative error associated with conformational averaging can help to determine the minimum number of replicas to be simulated in the context of M&M simulations. Altogether our data provides useful indication on how to generate sound conformational ensemble in agreement with experimental data.
  • Access State: Open Access