Conservation of closed loops.

The closed loop hypothesis of Berezovsky and Trifonov implicates the closure of loops of length 25-35 through hydrophobic interactions at the 'locks' as a key event in protein folding. The hypothesis is supported by published analyses of nine major superfolds. Here, we have generated multiple sequence alignments for the nine superfolds with PDB codes lthb, 1ilb, 256b, 2rhe, 1aps, 2stv, 4fxn (2fox), lubq and 7tim and have analysed the degree of conservation at the loop ends. Seventy percent of these loop ends are found to be well conserved and the peak in the distribution of distances between these well conserved regions lies at around 25 residues; both observations are consistent with the Berezovsky and Trifonov's hypothesis.