000013512 001__ 13512 000013512 005__ 20251007025657.0 000013512 02470 $$ahttps://doi.org/10.1021/acs.jctc.1c00609$$2doi 000013512 037__ $$aTEXTUAL 000013512 037__ $$bArticle 000013512 041__ $$aeng 000013512 245__ $$aUsing Constrained Density Functional Theory to Track Proton Transfers and to Sample Their Associated Free Energy Surface 000013512 269__ $$a2021-09-01 000013512 336__ $$aArticle 000013512 520__ $$aAb initio molecular dynamics (AIMD) and quantum mechanics/molecular mechanics (QM/MM) methods are powerful tools for studying proton solvation, transfer, and transport processes in various environments. However, due to the high computational cost of such methods, achieving sufficient sampling of rare events involving excess proton motion—especially when Grotthuss proton shuttling is involved—usually requires enhanced free energy sampling methods to obtain informative results. Moreover, an appropriate collective variable (CV) that describes the effective position of the net positive charge defect associated with an excess proton is essential both for tracking the trajectory of the defect and for the free energy sampling of the processes associated with the resulting proton transfer and transport. In this work, such a CV is derived from first principles using constrained density functional theory (CDFT). This CV is applicable to a broad array of proton transport and transfer processes as studied via AIMD and QM/MM simulations. 000013512 536__ $$oNational Institute of General Medical Sciences$$cR01 GM053148 000013512 536__ $$oU.S. Department of Energy$$cDE-SC0018648 000013512 540__ $$a<p>© 2021 The Authors.</p> <p>This publication is licensed under <a href="https://creativecommons.org/licenses/by/4.0/">CC-BY 4.0</a>.</p> 000013512 542__ $$fCC BY 000013512 690__ $$aPhysical Sciences Division 000013512 691__ $$aChemistry 000013512 692__ $$aChicago Center for Theoretical Chemistry 000013512 692__ $$aInstitute for Biophysical Dynamics 000013512 692__ $$aJames Franck Institute 000013512 7001_ $$aLi, Chenghan$$uUniversity of Chicago 000013512 7001_ $$1https://orcid.org/0000-0002-3267-6748$$2ORCID$$aVoth, Gregory A.$$uUniversity of Chicago 000013512 773__ $$tJournal of Chemical Theory and Computation 000013512 8564_ $$yArticle$$9df40273f-9981-479b-8f2a-41539a94182f$$s1466689$$uhttps://knowledge.uchicago.edu/record/13512/files/li-voth-2021-using-constrained-density-functional-theory-to-track-proton-transfers-and-to-sample-their-associated-free.pdf$$ePublic 000013512 8564_ $$ySupporting information$$9fa324908-f121-4e45-8392-cebd08b9bcab$$s234246$$uhttps://knowledge.uchicago.edu/record/13512/files/5598592.zip$$ePublic 000013512 908__ $$aI agree 000013512 909CO $$ooai:uchicago.tind.io:13512$$pGLOBAL_SET 000013512 983__ $$aArticle