title: Single water entropy: hydrophobic crossover and application to drug binding.
abstract: Entropy of water plays an important role in both chemical and biological processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new approach to calculate translational and rotational entropy of the individual water molecules around different hydrophobic and charged solutes. We show that for small hydrophobic solutes, the translational and rotational entropies of each water molecule increase as a function of its distance from the solute reaching finally to a constant bulk value. As the size of the solute increases (0.746 nm), the behavior of the translational entropy is opposite; water molecules closest to the solute have higher entropy that reduces with distance from the solute. This indicates that there is a crossover in translational entropy of water molecules around hydrophobic solutes from negative to positive values as the size of the solute is increased. Rotational entropy of water molecules around hydrophobic solutes for all sizes increases with distance from the solute, indicating the absence of crossover in rotational entropy. This makes the crossover in total entropy (translation + rotation) of water molecule happen at much larger size (>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from the ellipsoid of inertia. We further discuss the origin of higher entropy of water around water and show the possibility of recovering the entropy loss of some hypothetical solutes. The results obtained are helpful to understand water entropy behavior around various hydrophobic and charged environments within biomolecules. Finally, we show how our approach can be used to calculate the entropy of the individual water molecules in a protein cavity that may be replaced during ligand binding.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research , Pune, India.
authors.forename: Wilbee D
authors.initials: WD
authors.lastname: Sasikala
authors.forename: Arnab
authors.initials: A
authors.lastname: Mukherjee
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D019277:Entropy; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008697:Methane / Q000737:chemistry; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D012399:Rotation; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D011506:Proteins; D012996:Solutions; D012997:Solvents; D014867:Water; D019809:Streptavidin; D008697:Methane; D010100:Oxygen