Quantification of solvent contribution to the stability of noncovalent complexes

Haiyang Zhang, Tianwei Tan, C. Hetényi, David Van Der Spoel

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)4542-4551
Number of pages10
JournalJournal of Chemical Theory and Computation
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 8 2013

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nabumetone
Solvation
Free energy
Entropy
Thermodynamics
Cyclodextrins
Complexation
Binding energy
solvation
Molecular dynamics
Enthalpy
flexibility
free energy
entropy
thermodynamics
Molecules
Water
Computer simulation
Pharmaceutical Preparations
drugs

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Science Applications

Cite this

Quantification of solvent contribution to the stability of noncovalent complexes. / Zhang, Haiyang; Tan, Tianwei; Hetényi, C.; Van Der Spoel, David.

In: Journal of Chemical Theory and Computation, Vol. 9, No. 10, 08.10.2013, p. 4542-4551.

Research output: Contribution to journalArticle

Zhang, Haiyang ; Tan, Tianwei ; Hetényi, C. ; Van Der Spoel, David. / Quantification of solvent contribution to the stability of noncovalent complexes. In: Journal of Chemical Theory and Computation. 2013 ; Vol. 9, No. 10. pp. 4542-4551.
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