title: Metadynamics combined with auxiliary density functional and density functional tight-binding methods: alanine dipeptide as a case study.
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 (ΔFeq-ax) of ∼ -3 kcal mol-1between the two low energy conformers, C7eqand C7ax, which is lower by only 1.5 kcal mol-1than the ΔFeq-axcomputed 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.
authors.affiliation: Laboratoire de Chimie et Physique Quantiques (LCPQ), Université de Toulouse III [UPS] and CNRS, 118 Route de Narbonne, 31062, Toulouse, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Cuny
authors.affiliation: Laboratoire de Chimie et Physique Quantiques (LCPQ), Université de Toulouse III [UPS] and CNRS, 118 Route de Narbonne, 31062, Toulouse, France.
authors.forename: Kseniia
authors.initials: K
authors.lastname: Korchagina
authors.affiliation: UMR 5253 CNRS/ENSCM/UM, MACS, Institut Charles Gerhardt Montpellier, 8 rue de l'Ecole Normale, 34296, Montpellier cedex 5, France.
authors.forename: Chemseddine
authors.initials: C
authors.lastname: Menakbi
authors.affiliation: UMR 5253 CNRS/ENSCM/UM, MACS, Institut Charles Gerhardt Montpellier, 8 rue de l'Ecole Normale, 34296, Montpellier cedex 5, France. tzonka.mineva@enscm.fr.
authors.forename: Tzonka
authors.identifier: http://orcid.org/0000-0002-9156-2396
authors.initials: T
authors.lastname: Mineva
mesh_terms: D000409:Alanine / Q000737:chemistry*; D055592:Biophysical Phenomena; D004151:Dipeptides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D004151:Dipeptides; D012997:Solvents; D014867:Water; D000409:Alanine
keywords: Alanine dipeptide; Auxiliary density functional theory; Free energy surface; Metadynamics; Tight-binding density functional theory