We have performed all atom simulations of blocked peptides of the form (AAXAA) 3 , where X 5 Gln, Asn, Glu, Asp, Arg, and Lys with explicit water molecules to examine the interactions between side chains spaced i,i-5 in the sequence. Although side chains in this i,i-5 arrangement are commonly believed to be noninteracting, we have observed the formation of unusual i,i-5 main chain hydrogen bonding in such sequences with positively charged residues (Lys) as well as polar uncharged groups (Gln). Our results are consistent with the unusual percentage of hydrogen bonding curves produced by amide exchange measurements on the well-studied sequence acetyl-(AAQAA) 3 -amide in water (Shalongo, W., Dugad, L., Stellwagen, E. J. Am. Chem. Soc. 116:8288-8293, 1994). Analysis of our simulations indicated that the glutamine side chain showed the greatest propensity to support p helix formation and that the i,i-5 intramolecular hydrogen bonds were stabilized by waterbridging side chain interactions. This intermittent formation of the unusual p helix structure was observed for up to 23% of the total simulation time in some residues in (AAQAA) 3 . Control studies on peptides with glutamine side chains spaced i,i-3, i,i-4, and i,i-6 did not reveal similar unique structures, providing stronger evidence for the unique role side chain interactions with i,i-5 spacing. Proteins 28:59-71, 1997