Capturing Deuteration Effects in a Molecular Mechanics Force Field: Deuterated THF and the THF–Water Miscibility Gap

Agarwal, Rupesh; Smith, Micholas Dean; Smith, Jeremy C.

doi:10.1021/acs.jctc.9b01138

Title: Capturing Deuteration Effects in a Molecular Mechanics Force Field: Deuterated THF and the THF–Water Miscibility Gap

Journal Article · Mon Mar 16 00:00:00 EDT 2020 · Journal of Chemical Theory and Computation

DOI:https://doi.org/10.1021/acs.jctc.9b01138· OSTI ID:1648944

^[1];

^[2];

^[2]

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). UT/ORNL Center for Molecular Biophysics; Univ. of Tennessee, Knoxville, TN (United States). Graduate School of Genome Science and Technology
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). UT/ORNL Center for Molecular Biophysics; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry and Cellular and Molecular Biology

Deuteration is a common chemical modification used in conjunction with experiments such as neutron scattering, NMR, and Fourier-transform infrared for the study of molecular systems. Under the Born–Oppenheimer (BO) approximation, while the underlying potential energy surface remains unchanged by isotopic substitutions, isotopic substitution still alters intramolecular vibrations, which in turn may alter intermolecular interactions. Molecular mechanics (MM) force fields used in classical molecular dynamics simulations are assumed to represent local approximations of the BO potential energy surfaces, and hence, MD simulations using simple isotopic mass substitutions should capture BO-compatible isotope effects. However, standard MM force-field parameterizations do not directly fit to the local harmonic quantum mechanical (QM) Hessian that describes the BO surface, but rather to QM normal-modes and/or mass-dependent internal-coordinate derived distortion energies. In this study, using tetrahydrofuran (THF)–water mixtures as our model system, we show that not only does a simple mass-substitution approach fail to capture an experimentally characterized deuteration effect (the loss of the closed-loop miscibility gap associated with the complete deuteration of THF) but also it is necessary to generate new MM force-field parameters that correctly describe isotopic dependent vibrations to capture the experimental deuteration effect. We show that the origin of this failure is a result of using mass-dependent features to fit the THF MM force field, which unintentionally biases the bonded terms of the force field to represent only the isotopologue used during the original force-field parameterization. In addition, we make use of our isotopologue-corrected force field for D₈THF to examine the molecular origins of the isotope-dependent loss of the THF–water miscibility gap.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-00OR22725; FWP-ERKP752

OSTI ID:: 1648944

Journal Information:: Journal of Chemical Theory and Computation, Vol. 16, Issue 4; ISSN 1549-9618

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 4 works

Citation information provided by
Web of Science

References (68)

Molecular motions in liquid crystal BBBA (4O.4): QENS study Mitra, S.; Mukhopadhyay, R.; Venu, K. Chemical Physics, Vol. 261, Issue 1-2 https://doi.org/10.1016/s0301-0104(00)00227-5	journal	November 2000
Selective Deuteration Reveals Interference Caused by Side-Chain Dynamics on Measurements of Self-Diffusion in Ionic Liquid Cations Panesar, Kuldeep S.; Judeinstein, Patrick; Zanotti, Jean-Marc Journal of the Physical Society of Japan, Vol. 82, Issue Suppl.A https://doi.org/10.7566/jpsjs.82sa.sa013	journal	January 2013
The study of biological structures by neutron scattering from solution Jacrot, B. Reports on Progress in Physics, Vol. 39, Issue 10 https://doi.org/10.1088/0034-4885/39/10/001	journal	October 1976
Dynamic structure of membranes by deuterium NMR Smith, R.; Oldfield, E. Science, Vol. 225, Issue 4659 https://doi.org/10.1126/science.6740310	journal	July 1984
Structural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR Roder, Heinrich; Elöve, Gülnur A.; Englander, S. Walter Nature, Vol. 335, Issue 6192 https://doi.org/10.1038/335700a0	journal	October 1988
Moisture uptake in native cellulose – the roles of different hydrogen bonds: a dynamic FT-IR study using Deuterium exchange Hofstetter, Karin; Hinterstoisser, Barbara; Salmén, Lennart Cellulose, Vol. 13, Issue 2 https://doi.org/10.1007/s10570-006-9055-2	journal	March 2006
Partially deuterated phospholipids as IR structure probes of conformational order in bulk and monolayer phases Gericke, Arne; Moore, David J.; Erukulla, Ravi Kumar Journal of Molecular Structure, Vol. 379, Issue 1-3 https://doi.org/10.1016/0022-2860(95)09201-3	journal	June 1996
Carbon−Deuterium Bonds as Probes of Dihydrofolate Reductase Thielges, Megan C.; Case, David A.; Romesberg, Floyd E. Journal of the American Chemical Society, Vol. 130, Issue 20 https://doi.org/10.1021/ja0779607	journal	May 2008
Efforts toward Developing Probes of Protein Dynamics: Vibrational Dephasing and Relaxation of Carbon–Deuterium Stretching Modes in Deuterated Leucine Zimmermann, Jörg; Gundogdu, Kenan; Cremeens, Matthew E. The Journal of Physical Chemistry B, Vol. 113, Issue 23 https://doi.org/10.1021/jp900516c	journal	June 2009
Fourier transform infrared difference spectroscopy of bacteriorhodopsin and its photoproducts regenerated with deuterated tyrosine Dollinger, Gavin; Eisenstein, Laura; Lin, Shuo Liang Biochemistry, Vol. 25, Issue 21 https://doi.org/10.1021/bi00369a028	journal	October 1986
Isotope effects in the electron spin resonance spectra of deuterated triphenylmethyl radicals Trapp, Charles; Kulkarni, Shrikant V. The Journal of Physical Chemistry, Vol. 88, Issue 13 https://doi.org/10.1021/j150657a007	journal	June 1984
Deuterated phospholipids as raman spectroscopic probes of membrane structure Mendelsohn, Richard; Koch, Charles C. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 598, Issue 2 https://doi.org/10.1016/0005-2736(80)90004-8	journal	May 1980
Geometric isotope effect of deuteration in a hydrogen-bonded host–guest crystal Shi, Chao; Zhang, Xi; Yu, Chun-Hua Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-02931-8	journal	February 2018
Effect of deuteration on hydrogen bonds Rao, C. N. Ramachandra Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, Vol. 71, Issue 0 https://doi.org/10.1039/f19757100980	journal	January 1975
Comparison of path integral molecular dynamics methods for the infrared absorption spectrum of liquid water Habershon, Scott; Fanourgakis, George S.; Manolopoulos, David E. The Journal of Chemical Physics, Vol. 129, Issue 7 https://doi.org/10.1063/1.2968555	journal	August 2008
Ab initio centroid path integral molecular dynamics: Application to vibrational dynamics of diatomic molecular systems Ohta, Yasuhito; Ohta, Koji; Kinugawa, Kenichi The Journal of Chemical Physics, Vol. 120, Issue 1 https://doi.org/10.1063/1.1626632	journal	January 2004
Quantum Rate Coefficients and Kinetic Isotope Effect for the Reaction Cl + CH ₄ → HCl + CH ₃ from Ring Polymer Molecular Dynamics Li, Yongle; Suleimanov, Yury V.; Green, William H. The Journal of Physical Chemistry A, Vol. 118, Issue 11 https://doi.org/10.1021/jp501043z	journal	March 2014
Chemical Reaction Rate Coefficients from Ring Polymer Molecular Dynamics: Theory and Practical Applications Suleimanov, Yury V.; Aoiz, F. Javier; Guo, Hua The Journal of Physical Chemistry A, Vol. 120, Issue 43 https://doi.org/10.1021/acs.jpca.6b07140	journal	September 2016
Effect of deuteration on the phase behaviour and structure of lamellar phases of phosphatidylcholines – Deuterated lipids as proxies for the physical properties of native bilayers Bryant, Gary; Taylor, Matthew B.; Darwish, Tamim A. Colloids and Surfaces B: Biointerfaces, Vol. 177 https://doi.org/10.1016/j.colsurfb.2019.01.040	journal	May 2019
Deuteron NMR relaxation, phase diagrams, and isotope effects in liquid mixtures of tetrahydrofuran/d2O/salt Balevicius, Vytautas; Weiden, Norbert; Weiss, Alarich Berichte der Bunsengesellschaft für physikalische Chemie, Vol. 98, Issue 6 https://doi.org/10.1002/bbpc.19940980605	journal	June 1994
Isotope effect on the coexistence curve and crossover behavior of water+tetrahydrofuran Oleinikova, Alla; Weingärtner, Hermann Chemical Physics Letters, Vol. 319, Issue 1-2 https://doi.org/10.1016/s0009-2614(00)00086-5	journal	March 2000
Scattering Density Profile Model of POPG Bilayers As Determined by Molecular Dynamics Simulations and Small-Angle Neutron and X-ray Scattering Experiments Kučerka, Norbert; Holland, Bryan W.; Gray, Chris G. The Journal of Physical Chemistry B, Vol. 116, Issue 1 https://doi.org/10.1021/jp208920h	journal	December 2011
Structural and mechanical properties of cardiolipin lipid bilayers determined using neutron spin echo, small angle neutron and X-ray scattering, and molecular dynamics simulations Pan, Jianjun; Cheng, Xiaolin; Sharp, Melissa Soft Matter, Vol. 11, Issue 1 https://doi.org/10.1039/c4sm02227k	journal	January 2015
Constant pressure path integral molecular dynamics studies of quantum effects in the liquid state properties of n -alkanes Balog, E.; Hughes, A. L.; Martyna, G. J. The Journal of Chemical Physics, Vol. 112, Issue 2 https://doi.org/10.1063/1.480614	journal	January 2000
Structure of Aqueous Proline via Parallel Tempering Molecular Dynamics and Neutron Diffraction Troitzsch, R. Z.; Martyna, G. J.; McLain, S. E. The Journal of Physical Chemistry B, Vol. 111, Issue 28 https://doi.org/10.1021/jp0714973	journal	July 2007
Isotope effects in water as investigated by neutron diffraction and path integral molecular dynamics Zeidler, Anita; Salmon, Philip S.; Fischer, Henry E. Journal of Physics: Condensed Matter, Vol. 24, Issue 28 https://doi.org/10.1088/0953-8984/24/28/284126	journal	June 2012
Understanding How Isotopes Affect Charge Transfer in P3HT/PCBM: A Quantum Trajectory-Electronic Structure Study with Nonlinear Quantum Corrections Wang, Lei; Jakowski, Jacek; Garashchuk, Sophya Journal of Chemical Theory and Computation, Vol. 12, Issue 9 https://doi.org/10.1021/acs.jctc.6b00126	journal	August 2016
Eckart−Sayvetz conditions revisited Szalay, Viktor The Journal of Chemical Physics, Vol. 140, Issue 23 https://doi.org/10.1063/1.4883195	journal	June 2014
Vibrational spectra of deuterated methane and water molecules in structure I clathrate hydrate from ab initio MD simulation Hiratsuka, Masaki; Ohmura, Ryo; Sum, Amadeu K. Molecular Simulation, Vol. 41, Issue 10-12 https://doi.org/10.1080/08927022.2014.929125	journal	July 2014
Molecular Mechanics Vanommeslaeghe, Kenno; Guvench, Olgun; MacKerell, Alexander D. Current Pharmaceutical Design, Vol. 20, Issue 20 https://doi.org/10.2174/13816128113199990600	journal	May 2014
Robustness in the fitting of molecular mechanics parameters Vanommeslaeghe, Kenno; Yang, Mingjun; MacKerell, Alexander D. Journal of Computational Chemistry, Vol. 36, Issue 14 https://doi.org/10.1002/jcc.23897	journal	March 2015
Tetrahydrofuran complexes of transition metal chlorides Kern, R. J. Journal of Inorganic and Nuclear Chemistry, Vol. 24, Issue 9 https://doi.org/10.1016/0022-1902(62)80255-3	journal	December 1962
Thermodynamic Studies of Solid Polyethers. III. Poly(tetrahydrofuran), –[–(CH2)4O–;[ndash;n Yoshida, Shohei; Suga, Hiroshi; Seki, Syûzô Polymer Journal, Vol. 5, Issue 1 https://doi.org/10.1295/polymj.5.25	journal	October 1973
Enantiomer recognition of crown ethers and open-chain polyethers containing the trans-tetrahydrofuran-2,5-diylbis(methylene) subunit as the chiral centre Naemura, Koichiro; Ebashi, Iwao; Matsuda, Atsushi Journal of the Chemical Society, Chemical Communications, Issue 9 https://doi.org/10.1039/c39860000666	journal	January 1986
Synthesis and Characterization of Amphiphilic Polyethers Based on Tetrahydrofuran and Glycidol: Antibacterial Assessment Theiler, Stefan; Hövetborn, Thomas; Keul, Helmut Macromolecular Chemistry and Physics, Vol. 210, Issue 8 https://doi.org/10.1002/macp.200800502	journal	April 2009
THF co-solvent enhances hydrocarbon fuel precursor yields from lignocellulosic biomass Cai, Charles M.; Zhang, Taiying; Kumar, Rajeev Green Chemistry, Vol. 15, Issue 11 https://doi.org/10.1039/c3gc41214h	journal	January 2013
Local Phase Separation of Co-solvents Enhances Pretreatment of Biomass for Bioenergy Applications Mostofian, Barmak; Cai, Charles M.; Smith, Micholas Dean Journal of the American Chemical Society, Vol. 138, Issue 34 https://doi.org/10.1021/jacs.6b03285	journal	August 2016
Organosolv-Water Cosolvent Phase Separation on Cellulose and its Influence on the Physical Deconstruction of Cellulose: A Molecular Dynamics Analysis Smith, Micholas Dean; Cheng, Xiaolin; Petridis, Loukas Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-15048-7	journal	November 2017
A Multifunctional Cosolvent Pair Reveals Molecular Principles of Biomass Deconstruction Patri, Abhishek S.; Mostofian, Barmak; Pu, Yunqiao Journal of the American Chemical Society, Vol. 141, Issue 32 https://doi.org/10.1021/jacs.8b10242	journal	July 2019
Phase equilibria in binary mixtures. Part 2.—Miscibility gap with two critical temperatures (closed-loop phase diagram) Vnuk, František J. Chem. Soc., Faraday Trans. 2, Vol. 79, Issue 1 https://doi.org/10.1039/f29837900057	journal	January 1983
Reentrant phase transitions in multicomponent liquid mixtures Narayanan, T.; Kumar, Anil Physics Reports, Vol. 249, Issue 3 https://doi.org/10.1016/0370-1573(94)90015-9	journal	December 1994
Molecular Driving Forces behind the Tetrahydrofuran–Water Miscibility Gap Smith, Micholas Dean; Mostofian, Barmak; Petridis, Loukas The Journal of Physical Chemistry B, Vol. 120, Issue 4 https://doi.org/10.1021/acs.jpcb.5b09770	journal	January 2016
Structural Characteristics of a 0.23 Mole Fraction Aqueous Solution of Tetrahydrofuran at 20 °C Bowron, Daniel T.; Finney, John L.; Soper, Alan K. The Journal of Physical Chemistry B, Vol. 110, Issue 41 https://doi.org/10.1021/jp064170v	journal	October 2006
The Structure of Liquid Tetrahydrofuran Bowron, Daniel T.; Finney, John L.; Soper, Alan K. Journal of the American Chemical Society, Vol. 128, Issue 15 https://doi.org/10.1021/ja0583057	journal	April 2006
Optimization of parameters for molecular dynamics simulation using smooth particle-mesh Ewald in GROMACS 4.5 Abraham, Mark J.; Gready, Jill E. Journal of Computational Chemistry, Vol. 32, Issue 9 https://doi.org/10.1002/jcc.21773	journal	April 2011
Additive and Classical Drude Polarizable Force Fields for Linear and Cyclic Ethers Vorobyov, Igor; Anisimov, Victor M.; Greene, Shannon Journal of Chemical Theory and Computation, Vol. 3, Issue 3 https://doi.org/10.1021/ct600350s	journal	March 2007
Isotope effects in molecular mechanics (MM2). Calculations deuterium compounds Allinger, Norman L.; Flanagan, Heather L. Journal of Computational Chemistry, Vol. 4, Issue 3 https://doi.org/10.1002/jcc.540040315	journal	October 1983
Rapid parameterization of small molecules using the force field toolkit Mayne, Christopher G.; Saam, Jan; Schulten, Klaus Journal of Computational Chemistry, Vol. 34, Issue 32 https://doi.org/10.1002/jcc.23422	journal	September 2013
Application of finite orthogonal polynomials to the thermal functions of harmonic oscillators. V. Isotope chemistry and molecular structure. Simplified theory of end atom isotope effects Bigeleisen, Jacob.; Ishida, Takanobu. Journal of the American Chemical Society, Vol. 95, Issue 19 https://doi.org/10.1021/ja00800a001	journal	September 1973
TopoGromacs: Automated Topology Conversion from CHARMM to GROMACS within VMD Vermaas, Josh V.; Hardy, David J.; Stone, John E. Journal of Chemical Information and Modeling, Vol. 56, Issue 6 https://doi.org/10.1021/acs.jcim.6b00103	journal	May 2016
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Molecular dynamics with coupling to an external bath Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F. The Journal of Chemical Physics, Vol. 81, Issue 8 https://doi.org/10.1063/1.448118	journal	October 1984
Canonical sampling through velocity rescaling Bussi, Giovanni; Donadio, Davide; Parrinello, Michele The Journal of Chemical Physics, Vol. 126, Issue 1 https://doi.org/10.1063/1.2408420	journal	January 2007
Polymorphic transitions in single crystals: A new molecular dynamics method Parrinello, M.; Rahman, A. Journal of Applied Physics, Vol. 52, Issue 12 https://doi.org/10.1063/1.328693	journal	December 1981
Molecular dynamics integration and molecular vibrational theory. III. The infrared spectrum of water Praprotnik, Matej; Janežič, Dušanka The Journal of Chemical Physics, Vol. 122, Issue 17 https://doi.org/10.1063/1.1884609	journal	May 2005
The Statistical Thermodynamics of Multicomponent Systems McMillan, William G.; Mayer, Joseph E. The Journal of Chemical Physics, Vol. 13, Issue 7 https://doi.org/10.1063/1.1724036	journal	July 1945
Thermodynamics of Hydrogen Bonding in Hydrophilic and Hydrophobic Media van der Spoel, David; van Maaren, Paul J.; Larsson, Per The Journal of Physical Chemistry B, Vol. 110, Issue 9 https://doi.org/10.1021/jp0572535	journal	March 2006
Hydrogen-Bond Kinetics in the Solvation Shell of a Polypeptide Xu, Huafeng; Berne, B. J. The Journal of Physical Chemistry B, Vol. 105, Issue 48 https://doi.org/10.1021/jp012749h	journal	December 2001
Can Water Polarizability Be Ignored in Hydrogen Bond Kinetics? Xu, Huafeng; Stern, Harry A.; Berne, B. J. The Journal of Physical Chemistry B, Vol. 106, Issue 8 https://doi.org/10.1021/jp013426o	journal	February 2002
Estimating Error in Diffusion Coefficients Derived from Molecular Dynamics Simulations Pranami, Gaurav; Lamm, Monica H. Journal of Chemical Theory and Computation, Vol. 11, Issue 10 https://doi.org/10.1021/acs.jctc.5b00574	journal	September 2015
Experimental study of dynamic isotope effects in molecular liquids: Detection of translation‐rotation coupling Holz, Manfred; Mao, Xi‐an; Seiferling, Dieter The Journal of Chemical Physics, Vol. 104, Issue 2 https://doi.org/10.1063/1.470863	journal	January 1996
The infrared spectra of deuterated tetrahydrofurans Palm, A.; Bissell, E. R. Spectrochimica Acta, Vol. 16, Issue 4 https://doi.org/10.1016/0371-1951(60)80040-9	journal	January 1960
Does ℏ Play a Role in Multidimensional Spectroscopy? Reduced Hierarchy Equations of Motion Approach to Molecular Vibrations Sakurai, Atsunori; Tanimura, Yoshitaka The Journal of Physical Chemistry A, Vol. 115, Issue 16 https://doi.org/10.1021/jp1095618	journal	April 2011
Molecular dynamics simulation for infrared spectroscopy with intramolecular forces from electronic properties of on-the-fly quantum chemical calculations Ueno, Seiji; Tanimura, Yoshitaka; Ten-no, Seiichiro International Journal of Quantum Chemistry, Vol. 113, Issue 3 https://doi.org/10.1002/qua.24179	journal	June 2012
Deuterated drugs; updates and obviousness analysis Timmins, Graham S. Expert Opinion on Therapeutic Patents, Vol. 27, Issue 12 https://doi.org/10.1080/13543776.2017.1378350	journal	September 2017
FDA approves first drug for primary progressive multiple sclerosis Mullard, Asher Nature Reviews Drug Discovery, Vol. 16, Issue 5 https://doi.org/10.1038/nrd.2017.88	journal	May 2017
2H-NMR Study and Molecular Dynamics Simulation of the Location, Alignment, and Mobility of Pyrene in POPC Bilayers Hoff, Barbara; Strandberg, Erik; Ulrich, Anne S. Biophysical Journal, Vol. 88, Issue 3 https://doi.org/10.1529/biophysj.104.052399	journal	March 2005
Arabinose substitution effect on xylan rigidity and self-aggregation Shrestha, Utsab R.; Smith, Sydney; Pingali, Sai Venkatesh Cellulose, Vol. 26, Issue 4 https://doi.org/10.1007/s10570-018-2202-8	journal	January 2019

Similar Records

A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water

Journal Article · Mon Mar 21 00:00:00 EDT 2016 · Journal of Chemical Physics · OSTI ID:1648944

Schwörer, Magnus; Wichmann, Christoph; Tavan, Paul

Enabling quantitative analysis of complex polymer blends by infrared nanospectroscopy and isotopic deuteration

Journal Article · Tue Apr 04 00:00:00 EDT 2023 · Nanoscale · OSTI ID:1648944

Prine, Nathaniel; Cao, Zhiqiang; Zhang, Song; +7 more

Understanding How Isotopes Affect Charge Transfer in P3HT/PCBM: A Quantum Trajectory-Electronic Structure Study with Nonlinear Quantum Corrections

Journal Article · Tue Aug 09 00:00:00 EDT 2016 · Journal of Chemical Theory and Computation · OSTI ID:1648944

Wang, Lei; Jakowski, Jacek; Garashchuk, Sophya; +1 more

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
miscibility
peptides and proteins
diffusion
molecules
molecular mechanics

Title: Capturing Deuteration Effects in a Molecular Mechanics Force Field: Deuterated THF and the THF–Water Miscibility Gap

Citation Formats

References (68)

Similar Records

Related Subjects