We attempted three different strategies to obtain partial charges for the 2-hydroxypropyl substituted α-1,4-D glucopyranose. The first approach (A) relies on directly parameterizing the side chains of α-1,4-D glucopyranose for each of the seven possible sugars (see Table ). Here, we generated structures with the MCMM procedure available from the MacroModel 43 module in the Schrodinger package. We used the OPLS3e 42 force field and no solvent to generate suitable conformers. Individual conformers were rejected if they were too similar (measured as root mean squared deviation) to each other or formed strong intra-molecular hydrogen bonds between substituted side-chains. The latter was specifically done to avoid over-polarization in the charge-fitting procedure outlined below. The second approach (B) used 1-methoxypropan-2-ol (Figure ) as a model system for the 2hydroxypropyl side-chains in order to generalize our procedure. Suitable conformers were generated with MCMM as outlined above to obtain stable conformations. Our third approach (C) followed the original GLYCAM06 approach. Here, 1-methoxypropan-2-ol was parameterized with GAFF, AM1-BCC charges and solvated in a 14 Å water buffer of explicit TIP3P water in AMBER 16. This was followed by 5 ns of molecular dynamics simulation in the NPT ensemble at T = 300 K and P = 1 bar. From this simulation we extracted 100 snapshots used to fit a set of partial atomic charges.