The present application relates to a computer-implemented systems and methods for protein interaction design using surface fingerprints. The method comprises predicting at least one target interface site with high binding propensity, wherein, optionally, the step of predicting at least one target buried interface site comprises generating at least one surface fingerprint associated with a protein interaction based on at least one protein interface, wherein the at least one surface fingerprint preferably embeds geometric and/or chemical features of molecular surfaces, identifying at least one binding seed that displays required features to engage the target site, and performing a binding seed transplantation to protein scaffolds to confer stability and additional contacts on the designed interface.