title: Benchmark Study of the SCC-DFTB Approach for a Biomolecular Proton Channel.
abstract: The self-consistent charge density functional tight binding (SCC-DFTB) method has been increasingly applied to study proton transport (PT) in biological environments. However, recent studies revealing some significant limitations of SCC-DFTB for proton and hydroxide solvation and transport in bulk aqueous systems call into question its accuracy for simulating PT in biological systems. The current work benchmarks the SCC-DFTB/MM method against more accurate DFT/MM by simulating PT in a synthetic leucine-serine channel (LS2), which emulates the structure and function of biomolecular proton channels. It is observed that SCC-DFTB/MM produces over-coordinated and less structured pore water, an over-coordinated excess proton, weak hydrogen bonds around the excess proton charge defect and qualitatively different PT dynamics. Similar issues are demonstrated for PT in a carbon nanotube, indicating that the inaccuracies found for SCC-DFTB are not due to the point charge based QM/MM electrostatic coupling scheme, but rather to the approximations of the semiempirical method itself. The results presented in this work highlight the limitations of the present form of the SCC-DFTB/MM approach for simulating PT processes in biological protein or channel-like environments, while providing benchmark results that may lead to an improvement of the underlying method.
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, USA.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, USA.
authors.forename: Jessica M J
authors.initials: JM
authors.lastname: Swanson
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, University of Chicago, 5735 S. Ellis Ave., Chicago, Illinois 60637, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
keywords: DFT; Density Functional Theory; LS2; Proton Transport; QM/MM; SCC-DFTB; Self-Consistent Charge Density Functional Tight Binding; synthetic Leucine-Serine channel
references.citation: Biophys J. 1999 Nov;77(5):2400-10
references.pmid: 10545343
references.citation: Phys Rev B Condens Matter. 1996 Jul 15;54(3):1703-1710
references.pmid: 9986014
references.citation: J Phys Chem A. 2007 Oct 25;111(42):10861-73
references.pmid: 17914769
references.citation: J Phys Chem B. 1998 Apr 30;102(18):3586-616
references.pmid: 24889800
references.citation: J Comput Chem. 2009 Jul 30;30(10):1545-614
references.pmid: 19444816
references.citation: Biophys J. 2003 Aug;85(2):864-75
references.pmid: 12885634
references.citation: Biophys J. 2007 Jan 1;92(1):61-9
references.pmid: 17056732
references.citation: J Phys Chem B. 2013 May 2;117(17):5165-79
references.pmid: 23566052
references.citation: J Phys Chem B. 2010 May 27;114(20):7047-55
references.pmid: 20455530
references.citation: J Am Chem Soc. 2011 Sep 28;133(38):14981-97
references.pmid: 21761868
references.citation: J Phys Chem B. 2008 Aug 7;112(31):9456-66
references.pmid: 18630857
references.citation: Biochim Biophys Acta. 2010 Feb;1804(2):342-51
references.pmid: 19679196
references.citation: J Phys Chem B. 2005 Sep 22;109(37):17715-33
references.pmid: 16853267
references.citation: J Chem Theory Comput. 2012 Nov 13;8(11):4293-4304
references.pmid: 23275762
references.citation: J Comput Chem. 2004 Aug;25(11):1400-15
references.pmid: 15185334
references.citation: J Chem Theory Comput. 2006 Sep;2(5):1370-8
references.pmid: 26626844
references.citation: J Am Chem Soc. 2006 Dec 20;128(50):16302-11
references.pmid: 17165785
references.citation: Science. 1988 May 27;240(4856):1177-81
references.pmid: 2453923
references.citation: Front Biosci. 2003 Sep 01;8:s1384-79
references.pmid: 12957836
references.citation: J Chem Theory Comput. 2013 Jan 8;9(1):338-54
references.pmid: 26589037
references.citation: Phys Chem Chem Phys. 2012 Jan 14;14(2):899-913
references.pmid: 22119893
references.citation: J Chem Theory Comput. 2012 Apr 10;7(4):931-948
references.pmid: 23204947
references.citation: J Phys Chem B. 2009 Sep 3;113(35):11959-64
references.pmid: 19663399
references.citation: Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
references.pmid: 9944570
references.citation: J Chem Phys. 2005 Jul 22;123(4):044505
references.pmid: 16095367
references.citation: J Chem Phys. 2005 Jan 1;122(1):14515
references.pmid: 15638682
references.citation: J Phys Chem B. 2008 Jan 17;112(2):467-82
references.pmid: 17999484
references.citation: J Chem Theory Comput. 2005 Nov;1(6):1176-84
references.pmid: 26631661
references.citation: J Chem Phys. 2010 Apr 21;132(15):154104
references.pmid: 20423165
references.citation: J Chem Theory Comput. 2013 Jul 9;9(7):3020-5
references.pmid: 26583983
references.citation: J Phys Chem A. 2006 Jan 19;110(2):548-63
references.pmid: 16405327
references.citation: J Chem Phys. 2011 May 21;134(19):194109
references.pmid: 21599046
references.citation: J Phys Chem B. 2011 May 26;115(20):6790-805
references.pmid: 21526802
references.citation: J Am Chem Soc. 2005 Nov 30;127(47):16660-7
references.pmid: 16305255
references.citation: Phys Rev A Gen Phys. 1988 Sep 15;38(6):3098-3100
references.pmid: 9900728
references.citation: J Phys Chem B. 2010 May 27;114(20):6922-31
references.pmid: 20426461
references.citation: J Phys Chem B. 2009 Jan 29;113(4):1127-31
references.pmid: 19123911