PNNL

Abstract

As peptoids (N-substituted glycines) continue to gain popularity as a class of biomimetic polymers, the importance and demand for accuracy in force fields for molecular simulations also grows. Building on the vacuum-optimized STEPs forcefield, here we present STEPs-SOL, a novel peptoid force field parameterization that effectively incorporates solvent effects to enhance the accuracy of peptoid simulations. The development of STEPs-SOL is predicated on the necessity of precise electrostatic modeling. This is accomplished through partial charge optimization and addresses the computational challenges associated with simulating non-bonded energies, which are influenced by both electrostatic charges and Lennard-Jones interactions. The proposed parameterization workflow relies on high-level quantum mechanical data, aiming to establish a force field that accurately replicates experimental outcomes without depending solely on a limited set of experimental equilibrium property data. This is achieved by evaluating the effects of conformational bias in RESP charge generation and resulting equilibrium cis/trans ratios of peptoid residues in various solvents and examining their consequential effects on peptoid architecture, thereby enhancing our understanding of peptoid structural dynamics. Collectively, these advancements support the development of robust, accurately modeled biomimetic polymers, paving the way for significant innovations in material science and biopolymer research.