We have previously presented fully automated quantum chemistry-based workflows for predicting the regioselectivity of EAS reactions and palladium-catalyzed Heck reactions . Following this work, we introduce a workflow that, given a SMILES string as input, identifies possible nucleophilic and electrophilic sites and individually attaches methyl cations or anions to calculate associated MCA or MAA. The input SMILES string is modified using a set of SMIRKS and RDKit , which can easily be adjusted to include/exclude certain functional groups. The nucleophilic sites include double/triple-bonded atoms, singly charged anions, atoms with lone pairs, and specific functional groups such as aldehydes, amides, amines, carbanions, carboxylic acids, cyanoalkyl/nitrile anions, enolates, esters, ethers, imines, isonitriles, ketones, nitranions, nitriles, and nitronates. The electrophilic sites include double/triple-bonded atoms, singly charged cations, and specific functional groups such as acyl halides, aldehydes, amides, anhydrides, carbocations, esters, imines, iminium ions, ketones, Michael acceptors, and oxonium ions. The calculated MCAs and MAAs are defined in Equations 2 and 3 as the negative energy difference (-∆E) of a nucleophile (Nuc) reacting with a methyl cation (CH + 3 ) and an electrophile (Elec) reacting with a methyl anion (CH - 3 ), respectively.