Figure : Parameterization of the buffer. Panel A shows the AWH friction metric as a function of buffer charge. Since the higher the friction metric is, the slower the sampling, the buffers should ideally be forced into a low charge region. Panel B shows the density distribution of buffers in a membrane system. Optimized buffers do not penetrate into the lipid bilayer, while uncharged sodium ions do. Panel C shows the radial distribution function between buffers. When standard sodium ion parameters are used as buffers, the tendency to form clusters is high. Optimization of buffer parameters prevents clustering. Panel D shows the radial distribution functions of buffers to protein. The original sodium parameters again led to a much higher tendency of buffer to bind to the protein than that observed with optimized parameters.