Exploring the conformational and reactive dynamics of biomolecules in solution using an extended version of the glycine reactive force field

Abstract

In order to describe possible reaction mechanisms involving amino acids, and the evolution of the protonation state of amino acid side chains in solution, a reactive force field (ReaxFF-based description) for peptide and protein simulations has been developed as an expansion of the previously reported glycine parameters. This expansion consists of adding to the training set more than five hundred molecular systems, including all the amino acids and some short peptide structures, which have been investigated by means of quantum mechanical calculations. The performance of this ReaxFF protein force field on a relatively short time scale (500 ps) is validated by comparison with classical non-reactive simulations and experimental data of well characterized test cases, comprising capped amino acids, peptides, and small proteins, and reaction mechanisms connected to the pharmaceutical sector. A good agreement of ReaxFF predicted conformations and kinetics with reference data is obtained.

The ReaxFF reactive force-field: development, applications and future directions

“…39,45 Notable developments on the aqueous branch include water-liquid and proton/anion transfer extensions to a range of transition metals and metal oxides (Fe/Ni/Cu/Zn/Al/Ti/ Ca/Si), 7,15,19,35,46-52 along with C/H/O/N/S/P developments aimed at biomolecules and their interactions with inorganic interfaces. [53][54][55][56][57][58][59][60] Comparison to similar methods Although in this article we focus almost exclusively on ReaxFF and its applications, the ReaxFF method is not unique in its aim: to provide a simulation environment for describing the dynamics of chemical reactions at an atomistic scale with significantly fewer computational resources compared with QM. Purely empirical methods essentially abandon-or simplify-QM concepts, 61 providing significantly more freedom in their choice of functional form.…”

“…Rahaman et al 54,116 developed a ReaxFF description capable of modelling glycine tautomerisation in water, which was later employed to investigate the interaction between glycine and TiO 2 surfaces. 54 Monti et al 53 further extended this parameter set to include amino acids and short peptide structures, allowing ReaxFF to simulate the conformational dynamics of biomolecules in solution (Figure 4g). Aqueous proton transfer across graphene was investigated by Achtyl et al, 51 where ReaxFF helped to establish that proton transfer is enabled by hydroxyl-terminated atomic defects in the graphene sheet (Figure 4h).…”

Decoration of gold nanoparticles with cysteine in solution: reactive molecular dynamics simulations

“…23 In the previous study, 23 a new reactive force field was accurately parametrized to reproduce the interaction of cysteine (well parametrized in the gas phase, 24 on titania 25 and in water 26 ) with gold. Then, an effective molecular dynamics strategy was employed to observe migration of the molecule from solution to the (111) interface, its physisorption and the formation of a covalent bond between sulfur and gold ( preceded by the cleavage of the S-H bond).…”

On-the-Fly ab Initio Semiclassical Calculation of Glycine Vibrational Spectrum

“…Remarkably, the calculated frequencies are within 20–30 cm –1 of the experiments performed at 13 K. 12 Finally, a comprehensive set of studies concerning the four most stable glycine conformers has been recently presented by Barone and co-workers, ranging from purely spectroscopical studies 9,19 to reaction dynamics. 20 In their spectra simulations, Barone et al adopted the VPT2 approach with variational treatment of resonances (the so-called deperturbed second-order vibrational perturbation theory (DVPT2) 21,22 ) associated with a fourth-order representation of the PES computed at the DFT/B3LYP level of theory with medium sized basis sets. The calculated frequencies are in excellent agreement with experimental data from ref (12).…”