Many methods have been developed to analyse protein sequences and structure
s, although less work has been undertaken describing and comparing protein
surfaces. Evolution can lead sequences to diverge or structures to change t
opology; nevertheless, surface determinants that are essential to protein f
unction itself may be mantained. Moreover, different molecules could conver
ge to similar functions by gaining specific surface determinants. In such c
ases, sequence or structure comparisons are likely to be inadequate in desc
ribing or identifying protein functions and evolutionary relationships amon
g proteins. Surface analysis can identify function determinants that are in
dependent of sequence or secondary structure and can therefore be a powerfu
l tool to highlight cases of possible convergent or divergent evolution. Th
is kind of approach can be useful for a better understanding of protein mol
ecular and biochemical mechanisms of catalysis or interaction with a ligand
, which. are usually surface dependent. Protein surface comparison, when co
mpared to sequence or structure comparison methods, is a hard computational
challenge and evaluated methods allowing the comparison of protein surface
s are difficult to find. In this review, we will survey the current knowled
ge about protein surface similarity and the techniques to detect it.