D-amino acids are largely excluded from protein synthesis, yet they are of great interest in biotechnology. Aspartyl-tRNA synthetase (AspRS) can misacylate tRNA(Asp) with D-aspartate instead of its usual substrate, L-Asp. We investigate how the preference for L-Asp arises, using molecular dynamics simulations. Asp presents a special problem, having pseudosymmetry broken only by its ammonium group, and AspRS must protect not only against D-Asp, but against an "inverted" orientation where the two substrate carboxylates are swapped. We compare L-Asp and D-Asp, in both orientations, and succinate, where the ammonium group is removed and the ligand has an additional negative charge. All possible ammonium positions on the ligand are thus scanned, providing information on electrostatic interactions. As controls, we simulate a Q199E mutation, obtaining a reduction in binding free energy in agreement with experiment, and we simulate TyrRS, which can misacylate tRNA(Tyr) with D-Tyr. For both TyrRS and AspRS, we obtain a moderate binding free energy difference DeltaDeltaG between the L- and D-amino acids, in agreement with their known ability to misacylate their tRNAs. In contrast, we predict that AspRS is strongly protected against inverted L-Asp binding. For succinate, kinetic measurements reveal a DeltaDeltaG of over 5 kcal/mol, favoring L-Asp. The simulations show how chiral discriminations arises from the structures, with two AspRS conformations acting in different ways and proton uptake by nearby histidines playing a role. A complex network of charges protects AspRS against most binding errors, making the engineering of its specificity a difficult challenge.