Microsolvation of a polyalanine chain in a fully extended structure (FES) and polyproline II conformation (PP-II) is studied using density functional theory. Infinitely long systems are investigated to form infinite networks of hydrogen bonds (hbs) along the microsolvation shells. In this manner hbs cooperative effect is evaluated. The stability of microsolvated PP-II respect to microsolvated FES is investigated by changing the number of adsorbed water molecules per residue (nw) from 2 to 11. It is found that PP-II stability strongly depends on the nw value. For example, PP-II is more stable respect to FES by ∼14 kcal/mol for nw = 9, however its stability drops to ∼4 kcal/mol for nw = 10. It is shown that such behavior is connected to cooperative effects at the hydration shell, where water-water hbs strengthen up to 46%. Besides backbone-water hbs weaken, most notably in FES where its strength is diminished by 36%. Such interplay between water-water and backbone-water hydrogen bonding leads to a marginal stability of PP-II respect to FES for nw ≥ 10. © 2012 Wiley Periodicals, Inc.