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Acetic_acid_torsional_preferences.pdf (531.46 kB)
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Assessing the Conformational Equilibrium of Carboxylic Acid via QM and MD Studies on Acetic Acid

preprint
submitted on 21.11.2018 and posted on 23.11.2018 by Victoria T. Lim, Christopher I. Bayly, Laszlo Fusti-Molnar, David Mobley
Accurate hydrogen placement in molecular modeling is crucial for studying the interactions and dynamics of biomolecular systems. It is difficult to locate hydrogen atoms from many experimental structural characterization approaches, such as due to the weak scattering of x-ray radiation. Hydrogen atoms are usually added and positioned in silico when preparing experimental structures for modeling and simulation. The carboxyl functional group is a prototypical example of a functional group that requires protonation during structure preparation. To our knowledge, when in their neutral form, carboxylic acids are typically protonated in the syn conformation by default in classical molecular modeling packages, with no consideration of alternative conformations, though we are not aware of any careful examination of this topic. Here, we investigate the general belief that carboxylic acids should always be protonated in the syn conformation. We calculate and compare the relative energetic stabilities of syn and anti acetic acid using ab initio quantum mechanical calculations and atomistic molecular dynamics simulations. We show that while the syn conformation is the preferred state, the anti state may in some cases also be present under normal NPT conditions in solution.

Funding

The authors thank Prof. Filipp Furche and Matthew Agee for helpful discussions on QM methods and for support in using the Turbomole software package, respectively. VTL acknowledges funding the National Science Foundation Graduate Research Fellowship Program. DLM appreciates nancial support from the National Institutes of Health (1R01GM108889-01) and the National Science Foundation (CHE 1352608), and computing support from the UCI GreenPlanet cluster, supported in part by NSF Grant CHE-0840513.

History

Email Address of Submitting Author

limvt@uci.edu

Institution

University of California, Irvine

Country

United States

ORCID For Submitting Author

0000-0003-4030-9312

Declaration of Conflict of Interest

No conflict of interest

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