{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T21:03:59Z","timestamp":1771362239255,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431F 2020\/05, ED431C 2017\/25, and Centro singular de investigaci\u00f3n de Galicia accredita-tion 2016-2019, ED431G\/09"],"award-info":[{"award-number":["ED431F 2020\/05, ED431C 2017\/25, and Centro singular de investigaci\u00f3n de Galicia accredita-tion 2016-2019, ED431G\/09"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agencia Estatal de Investigaci\u00f3n (Ministerio)","award":["RTI2018-098795-A-I00, and PID2019-111327GB-I00, RYC-2016-20335"],"award-info":[{"award-number":["RTI2018-098795-A-I00, and PID2019-111327GB-I00, RYC-2016-20335"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["POCI-01-0145-30579"],"award-info":[{"award-number":["POCI-01-0145-30579"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Self-assembled cyclic peptide nanotubes with alternating D- and L-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 D,L-\u03b1-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\u20137 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.<\/jats:p>","DOI":"10.3390\/ijms23063158","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T03:34:13Z","timestamp":1647401653000},"page":"3158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison"],"prefix":"10.3390","volume":"23","author":[{"given":"Daniel","family":"Conde","sequence":"first","affiliation":[{"name":"Center for Research in Biological Chemistry and Molecular Materials, Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Santiago de Compostela, Campus Vida s\/n, 15782 Santiago de Compostela, Spain"},{"name":"Departamento de F\u00edsica Aplicada, Facultade de F\u00edsica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Pablo F.","family":"Garrido","sequence":"additional","affiliation":[{"name":"Departamento de F\u00edsica Aplicada, Facultade de F\u00edsica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-1781","authenticated-orcid":false,"given":"Mart\u00edn","family":"Calvelo","sequence":"additional","affiliation":[{"name":"Center for Research in Biological Chemistry and Molecular Materials, Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Santiago de Compostela, Campus Vida s\/n, 15782 Santiago de Compostela, Spain"},{"name":"Departament de Qu\u00edmica Inorg\u00e1nica i Org\u00e0nica and Institut de Qu\u00edmica Te\u00f2rica i Computacional (IQTCUB), Universitat de Barcelona, 08028 Barcelona, Spain"}]},{"given":"\u00c1ngel","family":"Pi\u00f1eiro","sequence":"additional","affiliation":[{"name":"Departamento de F\u00edsica Aplicada, Facultade de F\u00edsica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Rebeca","family":"Garcia-Fandino","sequence":"additional","affiliation":[{"name":"Center for Research in Biological Chemistry and Molecular Materials, Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Santiago de Compostela, Campus Vida s\/n, 15782 Santiago de Compostela, Spain"},{"name":"CIQUP, Centro de Investiga\u00e7\u00e3o em Qu\u00edmica, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4196-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Claro, B., Bastos, M., and Garcia-Fandino, R. 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