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Metadynamics combined with auxiliary density functional and density functional tight-binding methods: alanine dipeptide as a case study

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Abstract

Application of ab initio molecular dynamics to study free energy surfaces (FES) is still not commonly performed because of the extensive sampling required. Indeed, it generally necessitates computationally costly simulations of more than several hundreds of picoseconds. To achieve such studies, efficient density functional theory (DFT) formalisms, based on various levels of approximate computational schemes, have been developed, and provide a good alternative to commonly used DFT implementations. We report benchmark results on the conformational change FES of alanine dipeptide obtained with auxiliary density functional theory (ADFT) and second- and third-order density functional tight-binding (DFTB) methods coupled to metadynamics simulations. The influence of an explicit water solvent is also studied with DFTB, which was made possible by its lower computational cost compared to ADFT. Simulations lengths of 2.1 and 15 ns were achieved with ADFT and DFTB, respectively, in a reasonably short computational time. ADFT leads to a free energy difference (ΔF eq-ax) of ∼ −3 kcal mol−1 between the two low energy conformers, C7eq and C7ax, which is lower by only 1.5 kcal mol−1 than the ΔF eq-ax computed with DFTB. The two minima in ADFT FES are separated by an energy barrier of 9 kcal mol−1, which is higher than the DFTB barriers by 2–4 kcal mol−1. Despite these small quantitative differences, the DFTB method reveals FES shapes, confor-mation geometries and energies of the stationary points in good agreement with these found with ADFT. This validates the promising applicability of DFTB to FES of reactions occurring in larger-size systems placed in complex environments.

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Acknowledgements

The authors acknowledge the supercomputing facility of CALMIP for generous allocation of computer resources (projects P1320) and HPC resources from GENCI (Grant x2016087369). We also thank the PLUMED developers for their help and advice in plugging PLUMED 2 into deMon2k and deMonNano.

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Authors and Affiliations

  1. Laboratoire de Chimie et Physique Quantiques (LCPQ), Université de Toulouse III [UPS] and CNRS, 118 Route de Narbonne, 31062, Toulouse, France

    Jerome Cuny & Kseniia Korchagina

  2. UMR 5253 CNRS/ENSCM/UM, MACS, Institut Charles Gerhardt Montpellier, 8 rue de l’Ecole Normale, 34296, Montpellier cedex 5, France

    Chemseddine Menakbi & Tzonka Mineva

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  1. Jerome Cuny
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  2. Kseniia Korchagina
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  3. Chemseddine Menakbi
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  4. Tzonka Mineva
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Correspondence to Tzonka Mineva.

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This paper belongs to Topical Collection Festschrift in Honor of Henry Chermette

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Cuny, J., Korchagina, K., Menakbi, C. et al. Metadynamics combined with auxiliary density functional and density functional tight-binding methods: alanine dipeptide as a case study. J Mol Model 23, 72 (2017). https://doi.org/10.1007/s00894-017-3265-4

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