Extension of the Effective Fragment Potential Method to Macromolecules

Abstract

The effective fragment potential (EFP) approach, which can be described as a nonempirical polarizable force field, affords an accurate first-principles treatment of noncovalent interactions in extended systems. EFP can also describe the effect of the environment on the electronic properties (e.g., electronic excitation energies and ionization and electron-attachment energies) of a subsystem via the QM/EFP (quantum mechanics/EFP) polarizable embedding scheme. The original formulation of the method assumes that the system can be separated, without breaking covalent bonds, into closed-shell fragments, such as solvent and solute molecules. Here, we present an extension of the EFP method to macromolecules (mEFP). Several schemes for breaking a large molecule into small fragments described by EFP are presented and benchmarked. We focus on the electronic properties of molecules embedded into a protein environment and consider ionization, electron-attachment, and excitation energies (single-point calculations only). The model systems include chromophores of green and red fluorescent proteins surrounded by several nearby amino acid residues and phenolate bound to the T4 lysozyme. All mEFP schemes show robust performance and accurately reproduce the reference full QM calculations. For further applications of mEFP, we recommend either the scheme in which the peptide is cut along the Cα-C bond, giving rise to one fragment per amino acid, or the scheme with two cuts per amino acid, along the Cα-C and Cα-N bonds. While using these fragmentation schemes, the errors in solvatochromic shifts in electronic energy differences (excitation, ionization, electron detachment, or electron-attachment) do not exceed 0.1 eV. The largest error of QM/mEFP against QM/EFP (no fragmentation of the EFP part) is 0.06 eV (in most cases, the errors are 0.01-0.02 eV). The errors in the QM/molecular mechanics calculations with standard point charges can be as large as 0.3 eV.

Solvation effect on the vertical ionization energy of adenine‐thymine base pair: From microhydration to bulk

“…[6,10] The second category of methods uses explicit solvent molecules to incorporate the solute-solvent interactions and can take care of the short-range explicit interactions missing in the implicit solvent models. Krylov and co-workers extended the EFP method [5,11,[17][18][19][20][21] to accurate electronic structure methods like EOM-CCSD. It comes with a steep computation cost, especially if the computations are performed in an ab-initio or DFT methods.…”

An interaction energy driven biased sampling technique: A faster route to ionization spectra in condensed phase

“…Effective fragment potential (EFP) is a sophisticated polarizable MM method, and it has been benchmarked for the prediction of properties such as IEs using a hybrid QM/EFP formalism . EFP describes the discrete molecules as a combination of static multipole moments and induced dipole moments to include both accurate electrostatics (Coulomb) and polarization interactions.…”

Multiscale Modelling:Hybrid Quantum Mechanics/Molecular Mechanics as an Example and some Recent Developments

“…Molecular tailoring approach (MTA) 32 , molecular fractionation by conjugate capping (MFCC) 26 , fragment molecular orbitals (FMO) 33 , and molecule in molecule 34 are some examples of the divide and conquer approaches that have been extremely successful. MFCC-like approaches have also been developed for hybrid QM/EFP very recently 35 . Other fields of development are towards faster and more accurate polarizable force fields.…”