Abstract

Next-generation molecular force fields deliver accurate descriptions of non-covalent interactions by employing more elaborate functional forms than their predecessors. Much work has been dedicated to improving the description of the electrostatic potential (ESP) generated by these force fields. A common approach to improving the ESP is by augmenting the point charges on each center with higher-order multipole moments. The resulting anisotropy greatly improves the directionality of the non-covalent bonding, with a concomitant increase in computational cost. In this work, we develop an efficient strategy for enumerating multipole interactions, by casting an efficient spherical harmonic based approach within a particle mesh Ewald (PME) framework. Although the derivation involves lengthy algebra, the final expressions are relatively compact, yielding an approach that can efficiently handle both finite and periodic systems without imposing any approximations beyond PME. Forces and torques are readily obtained, making our method well suited to modern molecular dynamics simulations.Aggregation simulated studies on Ewald Aggregation simulated studies on an efficient algorithm for multipole energies and derivatives based on spherical harmonics and extensions to particle mesh Amyloid β-sheet helix-rich Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic modulators of α-Synuclein aggregation as a emerging template for drug discovery in α-synucleinopathy interfering amyloidogenesis pathways.

Keywords

Ewald Aggregation, simulated studies, algorithm, multipole energies, spherical harmonics, extensions; particle mesh; Amyloid β-sheet helix-rich; Val-Gly-Gly-Ala-Thr-Thr-Thr-Gly-Val-Thr peptide mimic; modulators; α-Synuclein aggregation; emerging template; drug discovery; α-synucleinopathy; interfering amyloidogenesis pathways;