atomic decomposition of the protein solvation free energy and its application to amyloidbeta protein in water we report the development of an atomic decomposition method of the protein solvation free energy in water which ascribes global change in the solvation free energy to local changes in protein conformation as well as in hydration structure so far empirical decomposition analyses based on simple continuum solvation models have prevailed in the study of proteinprotein interactions proteinligand interactions as well as in developing scoring functions for computeraided drug design however the use of continuum solvation model suffers serious drawbacks since it yields the protein free energy landscape which is quite different from that of the explicit solvent model and since it does not properly account for the nonpolar hydrophobic effects which play a crucial role in biological processes in water herein we develop an exact and general decomposition method of the solvation free energy that overcomes these hindrances we then apply this method to elucidate the molecular origin for the solvation free energy change upon the conformational transitions of 42residue amyloidbeta protein a42 in water whose aggregation has been implicated as a primary cause of alzheimers disease we address why a42 protein exhibits a great propensity to aggregate when transferred from organic phase to aqueous phase