10.26434/chemrxiv.8126912.v1
Peter Reinholdt
Erik Kjellgren
Casper Steinmann
Jógvan Magnus Haugaard Olsen
Cost-Effective Potential for Accurate Polarizable Embedding Calculations in Protein Environments
2019
ChemRxiv
polarizable embedding
multiscale modeling
QM/MM
2019-06-19 17:01:47
article
https://chemrxiv.org/articles/Cost-Effective_Potential_for_Accurate_Polarizable_Embedding_Calculations_in_Protein_Environments/8126912
<div>The fragment-based polarizable embedding model combined with an appropriate electronic-structure method constitutes a highly efficient and accurate multiscale approach for computing spectroscopic properties of a central moiety including effects from its molecular environment through an embedding potential. There is, however, a comparatively high computational overhead associated with the computation of the embedding potential which is derived from first principles calculations on individual fragments of the environment. To reduce the computational cost associated with the calculation of embedding-potential parameters, we developed a set of amino-acid-specific transferable parameters tailored for large-scale polarizable embedding calculations that include proteins. The amino-acid-based parameters are obtained by simultaneously fitting to a set of reference electric potentials based on structures derived from a backbone-dependent rotamer library. The developed cost-effective polarizable protein potential (CP<sup>3</sup>) consists of atom-centered charges and isotropic dipole-dipole polarizabilities of the standard amino acids. In terms of reproduction of electric potentials, the CP<sup>3</sup> is shown to perform consistently and with acceptable accuracy across both small tripeptide test systems and larger proteins. We show, through applications on realistic protein systems, that acceptable accuracy can be obtained by using a pure CP<sup>3</sup> representation of the protein environment, thus altogether omitting the cost associated with the calculation of embedding-potential parameters. High accuracy comparable to the full fragment-based approach can be achieved through a mixed description where the CP<sup>3</sup> is used only to describe amino acids beyond a threshold distance from the central quantum part.</div>