Prediction of local thermodynamics of water in and around endo-functionalized molecular tube receptors: An approach using grid inhomogeneous solvation theory

Abstract

Water molecules in and around a receptor play a significant role in the guest/ligand binding process. Here, we discuss the waters’ role in the guest binding process of small miniature receptor endo-functionalized molecular tubes (host-1a and host-1b). We have portrayed this using classical molecular dynamics (MD) simulation and GIST methodology. Trajectories from MD simulation have been utilized in GIST methodology to estimate different localized thermodynamic parameters at different regions of these receptors. These small receptors reveal a surprisingly detailed solvation structure, thermodynamic pattern and offer comprehensive insights. The torus site with high water density is especially relevant within the receptor binding sites in the solvation structure. Water molecules are energetically unstable inside (i.e., torus and cavity regions) of these host molecules. This water instability offers some guest molecules extremely high binding affinities inside these host cavities. Also, we are curious to see the effect of electrostatic on these thermodynamic parameters. For this, we have used a nonpolar version of these host molecules in which all partial charges of the atomic sites of both these receptors are artificially set to zero. Every energetic and entropic solvation parameters are less perturbed for nonpolar host molecules than the corresponding regular host molecules. The water molecules inside the nonpolar host cavity are less strongly bound than the corresponding regular host molecules. Thus, the value of free energy for removing water molecules from a particular region of a purely nonpolar host molecule is more favorable than the corresponding regular host molecule.