Metadynamics combined with auxiliary density functional and density functional tight-binding methods: alanine...

Area of Science:

• Computational Chemistry
• Theoretical Chemistry
• Molecular Dynamics

Background:

• Studying free energy surfaces (FES) using ab initio molecular dynamics is computationally intensive, often requiring simulations exceeding hundreds of picoseconds.
• Efficient density functional theory (DFT) formalisms have been developed to overcome these computational limitations.

Purpose of the Study:

• To benchmark auxiliary density functional theory (ADFT) and density functional tight-binding (DFTB) methods for calculating the conformational change FES of alanine dipeptide.
• To assess the feasibility of using DFTB for FES studies in explicit water solvent.

Main Methods:

• Metadynamics simulations coupled with ADFT and DFTB (second- and third-order).
• Comparison of simulation lengths, free energy differences, and energy barriers between methods.
• Inclusion of explicit water solvent effects using the computationally less expensive DFTB method.

Main Results:

• Achieved simulation lengths of 2.1 ns (ADFT) and 15 ns (DFTB) in reasonable computational time.
• ADFT yielded a free energy difference (ΔF_eq-ax) of ~-3 kcal/mol, while DFTB yielded a comparable value ~1.5 kcal/mol lower.
• Energy barriers calculated by ADFT were higher by 2-4 kcal/mol compared to DFTB, with both methods showing good agreement in FES shapes and stationary point properties.

Conclusions:

• DFTB provides a computationally efficient and accurate approach for studying FES, comparable to ADFT.
• DFTB is a promising method for FES investigations of larger systems in complex environments, including explicit solvent effects.