PeerJ. 2016 May 03;4:e1994. doi: 10.7717/peerj.1994. eCollection 2016.
Towards a barrier height benchmark set for biologically relevant systems.
PeerJ
Jimmy C Kromann, Anders S Christensen, Qiang Cui, Jan H Jensen
Affiliations
Affiliations
- Department of Chemistry, University of Copenhagen , Copenhagen , Denmark.
- Department of Chemistry, University of Wisconsin-Madison , Madison, WI , United States.
PMID: 27168993
PMCID: PMC4860304 DOI: 10.7717/peerj.1994
Abstract
We have collected computed barrier heights and reaction energies (and associated model structures) for five enzymes from studies published by Himo and co-workers. Using this data, obtained at the B3LYP/6- 311+G(2d,2p)[LANL2DZ]//B3LYP/6-31G(d,p) level of theory, we then benchmark PM6, PM7, PM7-TS, and DFTB3 and discuss the influence of system size, bulk solvation, and geometry re-optimization on the error. The mean absolute differences (MADs) observed for these five enzyme model systems are similar to those observed for PM6 and PM7 for smaller systems (10-15 kcal/mol), while DFTB results in a MAD that is significantly lower (6 kcal/mol). The MADs for PMx and DFTB3 are each dominated by large errors for a single system and if the system is disregarded the MADs fall to 4-5 kcal/mol. Overall, results for the condensed phase are neither more or less accurate relative to B3LYP than those in the gas phase. With the exception of PM7-TS, the MAD for small and large structural models are very similar, with a maximum deviation of 3 kcal/mol for PM6. Geometry optimization with PM6 shows that for one system this method predicts a different mechanism compared to B3LYP/6-31G(d,p). For the remaining systems, geometry optimization of the large structural model increases the MAD relative to single points, by 2.5 and 1.8 kcal/mol for barriers and reaction energies. For the small structural model, the corresponding MADs decrease by 0.4 and 1.2 kcal/mol, respectively. However, despite these small changes, significant changes in the structures are observed for some systems, such as proton transfer and hydrogen bonding rearrangements. The paper represents the first step in the process of creating a benchmark set of barriers computed for systems that are relatively large and representative of enzymatic reactions, a considerable challenge for any one research group but possible through a concerted effort by the community. We end by outlining steps needed to expand and improve the data set and how other researchers can contribute to the process.
Keywords: Benchmarks; Enzyme mechanism; Semiempirical methods
References
- J Comput Chem. 2010 Jun;31(8):1707-14 - PubMed
- J Chem Theory Comput. 2011 May 10;7(5):1494-501 - PubMed
- J Chem Theory Comput. 2011 Feb 8;7(2):291-309 - PubMed
- J Chem Phys. 2015 Aug 28;143(8):084123 - PubMed
- J Cheminform. 2012 Aug 13;4(1):17 - PubMed
- J Phys Chem B. 2015 Jan 22;119(3):1062-82 - PubMed
- Chemistry. 2012 Jul 27;18(31):9612-21 - PubMed
- J Chem Phys. 2015 Aug 7;143(5):054107 - PubMed
- J Chem Theory Comput. 2008 Jul;4(7):1129-37 - PubMed
- J Chem Theory Comput. 2011 Sep 13;7(9):2929-36 - PubMed
- J Comput Chem. 2015 Apr 5;36(9):622-32 - PubMed
- J Phys Chem B. 2013 Jul 11;117(27):8075-84 - PubMed
- J Chem Theory Comput. 2016 Mar 8;12(3):1082-96 - PubMed
- J Phys Chem A. 2007 Jul 5;111(26):5678-84 - PubMed
- J Chem Theory Comput. 2014 Apr 8;10(4):1518-1537 - PubMed
- J Chem Theory Comput. 2013 Jan 8;9(1):338-54 - PubMed
- Chem Rev. 2015 Jun 24;115(12):5678-796 - PubMed
- J Phys Chem B. 2007 Feb 15;111(6):1253-5 - PubMed
- J Chem Theory Comput. 2010 Jan 12;6(1):107-26 - PubMed
- Biochemistry. 2007 Nov 20;46(46):13352-69 - PubMed
- J Comput Chem. 2009 Nov 30;30(15):2388-401 - PubMed
- J Chem Theory Comput. 2016 Mar 8;12(3):1097-120 - PubMed
- J Chem Theory Comput. 2015 Apr 14;11(4):1525-39 - PubMed
- J Mol Model. 2007 Dec;13(12):1173-213 - PubMed
- Phys Chem Chem Phys. 2006 May 7;8(17):1985-93 - PubMed
- J Chem Theory Comput. 2013 May 14;9(5):2151-5 - PubMed
- J Chem Theory Comput. 2015 Jan 13;11(1):332-42 - PubMed
- J Mol Model. 2013 Jan;19(1):1-32 - PubMed
- Bioorg Chem. 2007 Dec;35(6):444-57 - PubMed
- J Chem Theory Comput. 2013 Jul 9;9(7):3240-51 - PubMed
- J Chem Theory Comput. 2012 Apr 10;7(4):931-948 - PubMed
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