Benchmarking quantum mechanical methods for calculating reaction energies of reactions catalyzed by enzymes

Jitnapa Sirirak,Narin Lawan,Adrian J Mulholland,Marc W Van Der Kamp,Jeremy N Harvey

doi:10.7717/peerj-pchem.8

Jitnapa Sirirak, Narin Lawan + Show 3 more

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https://doi.org/10.7717/peerj-pchem.8

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Abstract

To assess the accuracy of different quantum mechanical methods for biochemical modeling, the reaction energies of 20 small model reactions (chosen to represent chemical steps catalyzed by commonly studied enzymes) were calculated. The methods tested included several popular Density Functional Theory (DFT) functionals, second-order Møller Plesset perturbation theory (MP2) and its spin-component scaled variant (SCS-MP2), and coupled cluster singles and doubles and perturbative triples (CCSD(T)). Different basis sets were tested. CCSD(T)/aug-cc-pVTZ results for all 20 reactions were used to benchmark the other methods. It was found that MP2 and SCS-MP2 reaction energy calculation results are similar in quality to CCSD(T) (mean absolute error (MAE) of 1.2 and 1.3 kcal mol−1, respectively). MP2 calculations gave a large error in one case, and are more subject to basis set effects, so in general SCS-MP2 calculations are a good choice when CCSD(T) calculations are not feasible. Results with different DFT functionals were of reasonably good quality (MAEs of 2.5–5.1 kcal mol−1), whereas popular semi-empirical methods (AM1, PM3, SCC-DFTB) gave much larger errors (MAEs of 11.6–14.6 kcal mol−1). These results should be useful in guiding methodological choices and assessing the accuracy of QM/MM calculations on enzyme-catalyzed reactions.

Highlights

Quantum chemical calculations, including calculations with combined quantum mechanics/molecular mechanics (QM/MM) methods, are increasingly important in computational enzymology (Amaro & Mulholland, 2018; Blomberg et al, 2014; Huggins et al, 2019; Lonsdale, Ranaghan & Mulholland, 2010b; Senn & Thiel, 2009; Van der Kamp & Mulholland, 2013)
The approach used in this work is comparable to procedures often applied in QM/MM calculations on enzyme reactions, for which reaction paths may be optimized with Density Functional Theory (DFT) methods, and corrected with single point ab initio calculations (Claeyssens et al, 2006; Hermann et al, 2009; Lawan et al, 2019; Van der Kamp et al, 2010)
The results show that CCSD(T)/aug-cc-pVDZ has the lowest mean absolute errors (MAEs) (0.87 kcal mol−1) followed by MP2/aug-cc-pVTZ, spin-component scaled MP2 (SCS-MP2)/aug-cc-pVDZ and SCS-MP2/aug-cc-pVTZ which have MAEs of 1.16, 1.34 and 1.45 kcal mol−1, respectively

Summary

Introduction

Quantum chemical calculations, including calculations with combined quantum mechanics/molecular mechanics (QM/MM) methods, are increasingly important in computational enzymology (Amaro & Mulholland, 2018; Blomberg et al, 2014; Huggins et al, 2019; Lonsdale, Ranaghan & Mulholland, 2010b; Senn & Thiel, 2009; Van der Kamp & Mulholland, 2013). Ranaghan et al, 2019; Lawan et al, 2019; Mata et al, 2008; Van der Kamp, Perruccio & Mulholland, 2008; Van der Kamp et al, 2010), e.g., to model systems containing tens of atoms, i.e., of the size used in cluster models or as the QM region in a typical QM/MM calculation on an enzyme Methods such as CCSD(T) offer the potential of ‘chemical accuracy’ (i.e., agreement with experiment to within ∼1 kcal mol−1) in quantum chemical calculations (Bennie et al, 2016; Bistoni et al, 2018; Claeyssens et al, 2011; Daniels et al, 2014; Dieterich et al, 2010; Hermann et al, 2009; Lawan et al, 2019; Mata et al, 2008; Mulholland, 2007; Ranaghan et al, 2019; Van der Kamp, Perruccio & Mulholland, 2008; Van der Kamp et al, 2010; Zhang & Valeev, 2012). We compare and test a variety of quantum chemical methods that are commonly applied to model enzyme reaction mechanisms

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