Developing accurate intramolecular force fields for conjugated systems through explicit coupling terms

Abstract

The accuracy of molecular mechanics force fields (FF) reveals critical for applications where precise molecular structures along a conformational sampling are required, as in the simulation of electronic spectroscopies. This implies abandoning generalized FFs in favor of specific FFs, with non-transferable parameters able to accurately describe the targeted species. A promising strategy in this direction consists in the so-called quantum mechanically derived FFs, in which the parameters are fitted onto reference data computed through quantum chemistry. However, in order to obtain a global set of parameters able to reliably describe the reference potential energy surface in different regions of the conformational space, the complexity of the analytical expressions of the FF becomes crucial. Regarding intramolecular interactions, the functional form of standard transferable FFs is restricted to terms that depend on only one internal coordinate. It will be shown that such models may reveal insufficient to describe systems as polyenic chains, where complex electronic effects, e.g. conjugation, intrinsically couple different ICs. We propose a functional form for intramolecular FFs, which includes explicit couplings between flexible dihedrals and stiff ICs (bonds and angles), being able to properly describe the geometrical changes arising not only from steric interactions, but also from conjugation effects, i.e. the change of bond orders induced by conformational changes. The parameterization of the coupled FFs is carried out by means of automated and efficient computational

Could Quantum Mechanical Properties Be Reflected on Classical Molecular Dynamics? The Case of Halogenated Organic Compounds of Biological Interest

“…This is the case of some vibrational modes: even if a very precise parameterization is done, coupled vibrational modes in very conjugated molecules are extremely hard to describe (Prandi et al, 2016;Andreussi et al, 2017). The difficulty of an accurate description is mirrored in the fact that most MD simulation programs do not couple molecular motions like a stretching mode with an angular bending or the stretching modes of two adjacent atom pairs (Andreussi et al, 2017;Cerezo et al, 2018). More precisely, all mentioned terms in Equation (1) are expressed as sums of contributions, each one depending on a single internal coordinate.…”

“…In this way, the off-diagonal terms (or hybrid terms) of the Hessian are not explicitly taken into account. Here, it is important to emphasize that it is mathematically and physically possible to derive parameters considering the cited couplings (Cerezo et al, 2018), but the implementation of a force-field functional form that describes the coupled terms can still not be done in many MD software.…”

“…It is evident that neither the best set of parameters can completely recover the electronic effects of a given molecule along an MD trajectory. Although some MD simulation programs are starting to be more flexible in terms of a forcefield functional implementation, like GROMACS and Moscito (Cerezo et al, 2018). There is a still long path to achieve the full force-field functional form flexibility.…”

Adiabatic-Molecular Dynamics Generalized Vertical Hessian Approach: A Mixed Quantum Classical Method To Compute Electronic Spectra of Flexible Molecules in the Condensed Phase

“…W g and W KL are selected weights, which are set according to the Joyce default values. 7,50,52,53,69 Further details about the parameterization are included in Section S2 of the Supporting Information (SI).…”

A machine learning based intramolecular potential for a flexible organic molecule

“…There is a wide range of methods available for tting bond, angle and dihedral parameters of the MM force eld to QM energies, gradients and Hessian matrices, [23][24][25][26][27][28] and these oen include extended functional forms such as cross-terms to account for coupling between internal coordinates. 29 However, for larger, more exible molecules, longer-range atomic interactions beyond the 1-4 interaction are also crucial in determining molecular conformation. For these molecules, a consistent, accurate approach to approximating the QM potential energy surface is key.…”