A novel method reveals that solvent water favors polyproline II over BETA-strand conformation in peptides and unfolded proteins: Conditional Hydrophobic Accessible Surface Area (CHASA) Abstract: In aqueous solution the ensemble of conformations sampled by peptides and unfolded proteins is largely determined by their interaction with water. It has been a long-standing goal to capture these solute-water energetics accurately and efficiently in calculations. Historically, accessible surface area (ASA) is one of the most useful approaches, but this method breaks down when applied to the solvation energetics of amphipathic peptides and proteins. Here we introduce a novel method in which hydrophobic ASA is determined after first positioning water oxygens in hydrogen-bonded orientations proximate to all accessible peptide/protein backbone N and O atoms. This conditional hydrophobic accessible surface area (termed CHASA) successfully differentiates between previously unexplained solvation energies in polyalanyl peptides. Using experimental data, the CHASA method was validated by predicting the PII and BETA-strand conformational preferences of non-proline residues in the coil library (i.e. non-ALPHA-helix, non-BETA-strand, non-BETA-turn library) derived from X-ray elucidated structures.