The optimization workflow used herein is called Force FieLd Optimization Workflow (FFLOW), which is a modular optimization toolbox containing structures and methods introduced by Gradient-based Optimization Workflow (GrOW) . The FFLOW software files, scripts for parameter conversion (Gromacs to Amber), steering scrips that manage, for example, the queuing system, used input files, and all simulation configurations are available on GitHub via . The density calculations were carried out using Gromacs , while the RCE were computed by Amber .