Non-local residue-residue contacts in proteins are more conserved than local ones

Non-covalent residue-residue contacts drive the folding of proteins and stabilize them. They may be local-i.e. involve residues that are close in sequence, or non-local. It has been suggested that, in most proteins, local contacts drive protein folding by providing crucial constraints of the conformational space, thus allowing proteins to fold. We compared residues that are involved in local contacts to residues that are involved in non-local contacts and found that, in most proteins, residues in non-local contacts are significantly more conserved evolutionarily than residues in local contacts. Moreover, non-local contacts are more structurally conserved: a contact between positions that are distant in sequence is more likely to exist in many structural homologues compared with a contact between positions that are close in sequence. These results provide new insights into the mechanisms of protein folding and may allow for better prediction of critical intra-chain contacts.Supplementary information: Supplementary data are available at Bioinformatics online.