Real vs calculated residue co-locations (from ). The relative frequency of real residue co-locations was determined by SeqX in 80 different protein structures and compared to the relative frequency of calculated co-locations in artificial, random protein sequences (C). The 200 possible residue pairs provided by the 20 amino acids were grouped into 4 subgroups on the basis of their mutual physico-chemical compatibility, i.e., favored (+) and un-favored (-) in respect of hydrophobicity and charge. (HP+, hydrophobe-hydrophobe and lipophobe-lipophobe; HP-, hydrophobe-lipophobe; CH+, positive-negative and hydrophobe-charged; CH-: positive-positive, negative-negative and lipophobe-charged interactions). The bars represent the mean ± SEM (n = 80 for real structures and n = 10 for artificial sequences). Student's t-test was applied to evaluate the results.