Do cooperative cycles of hydrogen bonding exist in proteins?
  The closure of cooperative chains of Hydrogen Bonding, HB, to form cycles can enhance cooperativity. Cycles of charge transfer can balance charge into and out of every site, eliminating the charge build-up that limits the cooperativity of open unidirectional cooperative chains. If cycles of cooperative HB exist in proteins, these could be expected to be significant in protein structure and function in ways described below. We find no mention of an example of this kind of cycle in the literature. We investigate whether cooperative HB cycles not traversing solvent, ligand or modified residues occur in proteins by means including search of Nuclear Magnetic Resonance spectroscopy entries of the Protein Data Bank.   For the direct interactions of inter-amide HB, when the energy associated with Natural Bond Orbital, NBO, steric exchange is deducted from that of NBO donor-acceptor interactions, the result is close to zero, so that HB is not primarily due to the sum of direct inter-amide NBO interactions. The NBO binding energy is primarily associated with the increase in resonance of the amides, a consequence of which is that the majority of the NBO binding energy is susceptible to variation by electrostatic field with component parallel or antiparallel to an amide C-N bond.   The question of what geometry most favours HB in amides is revisited with emphasis on the inequivalence of amide/carbonyl oxygen lone pairs.   A possible avenue for the design of HB-chaining polymers with improved stability is discussed. 
John N. Sharley
physics.chem-ph