Previously we had developed a technique to specify post-translational modifications to peptide sequences as substitutions of certain amino-acids by irregular substituents, with amino-acid connection points . For reaction SPL we also developed an easier way to specify directly in the irregular substituent how it is inserted into the regular peptide chains. This leads to a more concise way of showing multiple intermediate structures without having to re-define the entire enzyme-ligand complex over and over again with all the chains and substitutions. But the principle is the same: a molfile is created with InChI and the atoms in the molfile sorted in InChI order to match the atom numbers (with all hydrogensif anyat the end). This yields unambiguous canonical atom numbers used to define the amino-acid connection points, in pairs of amino-N and carboxy-C atom numbers. For example, I32 in the molfile has the amino-acid connection point at position (83, 80); and R109 at (62, 59) and so on. These connection points are then directly linked with a "bond" of type "amino-acid substitution site" to the chain by referencing the chain by its id (e.g. "LDH-A") and providing the position number in the sequence. And because this substitution method normally points from the biomolecules to the irregular structure substituted into it, the connection points pair is also referenced in the first position number. Since for brevity here we are allowing to connect the connection points directly into the peptide chain, the first position number is just the ordinal number of the current connection points pair, 1, 2, 3, and so on. So, for example, R109 is described as connecting to the LHA-A chain at position (1, 106), 1 because R109 is the first connection points moiety of our molfile (and it is the first one because its InChI atom number of the amino-N is the lowest of them all) and "106" is the position in the actual amino acid letter sequence which corresponds to what is labeled "R109" in the PDB file: The discrepancy between "R109" being at the actual position 106 seems confusing, and we are left to guess why exactly there is such discrepancy. This may be because Cook et al. were trying to reference well known position that are conventionally labeled R109 even though their own sequence has this at position 106. But this indirection is a good test case to show how Reaction SPL gives the flexibility to use authorcontrolled labels (in the connection points moiety name "R109") and yet unambiguous correct index numbers into the actual sequences, which happens to be 106.