Quantification of Solvent Contribution to the Stability of Noncovalent Complexes.

摘要: We introduce an indirect approach to estimate the solvation contributions thermodynamics of noncovalent complex formation through molecular dynamics simulation. This estimation is demonstrated by potential mean force and entropy calculations on binding process between β-cyclodextrin (host) four drug molecules puerarin, daidzin, daidzein, nabumetone (guest) in explicit water, followed a stepwise extraction individual enthalpy (ΔH) (ΔS) terms from total free energy. Detailed analysis energetics host-guest complexation demonstrates that flexibility partners solvation-related ΔH ΔS need be included explicitly for accurate thermodynamics. From this, our previous work solvent dependency energies (Zhang et al. J. Phys. Chem. B 2012, 116, 12684-12693), it follows neglecting host or guest flexibility, those employing implicit solvent, will not able systematically predict energies. The presented here can readily adopted obtaining deeper understanding mechanisms governing associations solution.