The obtained partial charges for the side chains R 1 , R 2 and R 3 for the three different approaches (A, B and C) are shown in Table . Multiple substitutions for C are done by combining side chains appropriately as discussed above. The fitted charges obtained for the multiple substitutions (4GR, 4GS, 4GT and 4GW) for approach A are presented in Table in the supporting information. For the ether oxygen (Os), the partial charges obtained for Table : Partial charges obtained for the three different side chains R 1 , R 2 and R 3 . the first side chain (R 1 ) are -0.65, -0.50 and -0.48 for A, B and C, respectively. The partial charges are fairly constant for the 1-methoxypropan-2-ol model approaches (B and C), but for approach A the partial charge is about -0.1 to -0.2 lower in magnitude hinting to more polarized charges. The same ether oxygen in the R 2 and R 3 side chains also show large deviations between approach A with partial charges of -0.83 and -0.82 compared with partial charges that are -0.48 to -0.49 in magnitude for approaches B and C. Compared with previous efforts for the GROMOS force field 31 also presented in Table , our charges for approach C deviate by no more 0.02 for the ether oxygen on the R 1 side chain and similar results are observed for both R 2 and R 3 . The charges of the carbon atoms show similar tendencies with the major difference being the C 1 atom which has a positive charge of 0.16 for approach C but 0.48 for approach A again hinting at some over-polarization during the charge fitting. Interestingly, the partial charges for the hydroxy group (OH) is fairly constant between all tested approaches and agrees well with previous work. In summary, approach C gives resulting charges comparable to earlier work and does not show any sign of over-polarization and is consistent with how charges are derived in GLYCAM06. For these reasons, the remainder of this work will only use the partial charges obtained from approach C.