Hydration free energies were calculated using Free Energy Perturbation (FEP) and Bennett Acceptance Ratio (BAR), following the protocol we have previously adopted and described in SI section 2.1. Briefly, in each case, simulations consisting of a single solute molecule in water were conducted, first decoupling Coulombic interactions and then LJ interactions. The coupling parameter l C for the Coulombic interactions was scaled linearly and assumed 21 equally-spaced values between 0 and 1; decoupling the LJ interactions was done over 59 states, with unevenlyspaced l LJ values between 0 and 1. At each state, we performed a steepest-descent minimization, BFGS minimization, 100 ps of NVT equilibration and 100 ps of NpT equilibration before collect-ing statistics for each state over 2 ns. Five independent production runs were performed for each amino acid.