Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison
Self-assembled cyclic peptide nanotubes with alternating <i>D</i>- and <i>L</i>-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antim...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/3158 |
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| author | Daniel Conde Pablo F. Garrido Martín Calvelo Ángel Piñeiro Rebeca Garcia-Fandino |
| author_facet | Daniel Conde Pablo F. Garrido Martín Calvelo Ángel Piñeiro Rebeca Garcia-Fandino |
| author_sort | Daniel Conde |
| collection | DOAJ |
| description | Self-assembled cyclic peptide nanotubes with alternating <i>D</i>- and <i>L</i>-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antimicrobial peptides. Molecular dynamics simulations can be used to characterize these systems with atomic resolution at different time scales, providing information that is difficult to obtain via wet lab experiments. However, the performance of classical force fields typically employed in the simulation of biomolecules has not yet been extensively tested with this kind of highly constrained peptide. Four different classical force fields (AMBER, CHARMM, OPLS, and GROMOS), using a nanotube formed by eight <i>D</i>,<i>L</i>-α-cyclic peptides inserted into a lipid bilayer as a model system, were employed here to fill this gap. Significant differences in the pseudo-cylindrical cavities formed by the nanotubes were observed, the most important being the diameter of the nanopores, the number and location of confined water molecules, and the density distribution of the solvent molecules. Furthermore, several modifications were performed on GROMOS54a7, aiming to explore acceleration strategies of the MD simulations. The hydrogen mass repartitioning (HMR) and hydrogen isotope exchange (HIE) methods were tested to slow down the fastest degrees of freedom. These approaches allowed a significant increase in the time step employed in the equation of the motion integration algorithm, from 2 fs up to 5–7 fs, with no serious changes in the structural and dynamical properties of the nanopores. Subtle differences with respect to the simulations with the unmodified force fields were observed in the concerted movements of the cyclic peptides, as well as in the lifetime of several H-bonds. All together, these results are expected to contribute to better understanding of the behavior of self-assembled cyclic peptide nanotubes, as well as to support the methods tested to speed up general MD simulations; additionally, they do provide a number of quantitative descriptors that are expected to be used as a reference to design new experiments intended to validate and complement computational studies of antimicrobial cyclic peptides. |
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| language | English |
| last_indexed | 2024-03-09T19:42:09Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-2a4eef2e79e3485899ce4308b4ad3d762023-11-24T01:33:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236315810.3390/ijms23063158Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical ComparisonDaniel Conde0Pablo F. Garrido1Martín Calvelo2Ángel Piñeiro3Rebeca Garcia-Fandino4Center for Research in Biological Chemistry and Molecular Materials, Departamento de Química Orgánica, Universidade de Santiago de Compostela, Campus Vida s/n, 15782 Santiago de Compostela, SpainDepartamento de Física Aplicada, Facultade de Física, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainCenter for Research in Biological Chemistry and Molecular Materials, Departamento de Química Orgánica, Universidade de Santiago de Compostela, Campus Vida s/n, 15782 Santiago de Compostela, SpainDepartamento de Física Aplicada, Facultade de Física, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainCenter for Research in Biological Chemistry and Molecular Materials, Departamento de Química Orgánica, Universidade de Santiago de Compostela, Campus Vida s/n, 15782 Santiago de Compostela, SpainSelf-assembled cyclic peptide nanotubes with alternating <i>D</i>- and <i>L</i>-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antimicrobial peptides. Molecular dynamics simulations can be used to characterize these systems with atomic resolution at different time scales, providing information that is difficult to obtain via wet lab experiments. However, the performance of classical force fields typically employed in the simulation of biomolecules has not yet been extensively tested with this kind of highly constrained peptide. Four different classical force fields (AMBER, CHARMM, OPLS, and GROMOS), using a nanotube formed by eight <i>D</i>,<i>L</i>-α-cyclic peptides inserted into a lipid bilayer as a model system, were employed here to fill this gap. Significant differences in the pseudo-cylindrical cavities formed by the nanotubes were observed, the most important being the diameter of the nanopores, the number and location of confined water molecules, and the density distribution of the solvent molecules. Furthermore, several modifications were performed on GROMOS54a7, aiming to explore acceleration strategies of the MD simulations. The hydrogen mass repartitioning (HMR) and hydrogen isotope exchange (HIE) methods were tested to slow down the fastest degrees of freedom. These approaches allowed a significant increase in the time step employed in the equation of the motion integration algorithm, from 2 fs up to 5–7 fs, with no serious changes in the structural and dynamical properties of the nanopores. Subtle differences with respect to the simulations with the unmodified force fields were observed in the concerted movements of the cyclic peptides, as well as in the lifetime of several H-bonds. All together, these results are expected to contribute to better understanding of the behavior of self-assembled cyclic peptide nanotubes, as well as to support the methods tested to speed up general MD simulations; additionally, they do provide a number of quantitative descriptors that are expected to be used as a reference to design new experiments intended to validate and complement computational studies of antimicrobial cyclic peptides.https://www.mdpi.com/1422-0067/23/6/3158cyclic peptidesantimicrobial peptidesself-assembled peptide nanotubesmolecular dynamicsforce fieldhydrogen mass repartitioning |
| spellingShingle | Daniel Conde Pablo F. Garrido Martín Calvelo Ángel Piñeiro Rebeca Garcia-Fandino Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison International Journal of Molecular Sciences cyclic peptides antimicrobial peptides self-assembled peptide nanotubes molecular dynamics force field hydrogen mass repartitioning |
| title | Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison |
| title_full | Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison |
| title_fullStr | Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison |
| title_full_unstemmed | Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison |
| title_short | Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison |
| title_sort | molecular dynamics simulations of transmembrane cyclic peptide nanotubes using classical force fields hydrogen mass repartitioning and hydrogen isotope exchange methods a critical comparison |
| topic | cyclic peptides antimicrobial peptides self-assembled peptide nanotubes molecular dynamics force field hydrogen mass repartitioning |
| url | https://www.mdpi.com/1422-0067/23/6/3158 |
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