Software development for calculation of molecular surface area and its application to hydrophobic interaction

Abstract

A novel method of calculating the water-accessible molecular surface area from the number of points generated on the molecular surface was developed. This method yielded a molecular surface area with high accuracy and speed. The molecular surface area of lecithin shows an excellent linear correlation with the logarithm of the critical micelle concentration for many lecithins having different acyl chains. The solution structure of oxyphenonium bromide estimated from the molecular surface area approach was close to that obtained from NMR. Furthermore, the change of molecular surface area, ΔS(HG), with docking of host and guest was defined and its calculation method was developed. Because both the host and the guest generally consist of hydrophilic and hydrophobic atomic groups, ΔS(HG) was divided into such four terms as ΔSoo(HG), ΔSow(HG), ΔSwo(HG), and ΔSww(HG). For instance, ΔSoo(HG) is the decrease in surface area with contact between the hydrophobic surfaces of the host and the guest. When the guest molecule was moved along the symmetry axis of cyclodextrin (CyD), the structure of a complex having the maximum value of ΔSoo(HG) corresponds with the crystal structure. The solution structures of several inclusion systems were predicted by this method. For various systems including α-CyD, β-CyD, γ-CyD, and aromatic and aliphatic guests, the maximum values of ΔSoo(HG) showed a good correlation with the logarithms of the binding constants. This relationship will be used for the prediction of the binding constants for CyD and other host-guest systems.