The present invention relates to computer-implemented methods for predicting catalytic activity for a candidate mutant enzyme comprising estimating the electrostatic component of the activation barrier for each of a plurality of conformations of each candidate mutant enzyme, for predicting catalytic activity for a candidate mutant enzyme using a machine learning model trained using data obtained using such methods, for providing a site directed mutagenesis potential map for an enzyme using the described methods, and for identifying a candidate enzyme with improved catalytic activity using the described methods. Related systems and computer-readable media are also described.