How the stabilization of INK4 tumor suppressor 3D structure evaluated by quantum chemical and molecular mechanics calculations corresponds well with experimental results: interplay of association enthalpy, entropy, and solvation effects

The Journal of Physical Chemistry. B
Michal OtyepkaPavel Hobza

Abstract

The folding free energy of the INK4c tumor suppressor core, consisting of 10 helices, was determined as the sum of gas-phase interaction enthalpy, gas-phase interaction entropy, and dehydration and hydration free energy. The interaction energy and the hydration free energy were determined using the nonempirical density functional theory (DFT) method, augmented by a dispersion-energy correction term, the semiempirical density-functional tight-binding method covering the dispersion energy, and the density functional theory/conductor-like screening model (DFT/COSMO) procedure, whereas the interaction entropy was calculated with the empirical Cornell et al. force field. Alternatively, all contributions were evaluated consistently using empirical methods. All the values of the interaction energy of helix pairs are stabilizing, and the dominant stabilizing terms stem from the London dispersion energy and, in the case of charged systems, the electrostatic energy. The stabilization energy of the core, determined as the difference of the energy of the core and 10 separate helices, amounts to approximately 450 kcal/mol. Systematically, the difference in the hydration free energy of a helix pair and its separate components is smaller in m...Continue Reading

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Citations

Nov 18, 2009·Journal of Biomolecular Structure & Dynamics·P Sklenovsý, M Otyepka
Sep 12, 2008·Journal of Computational Chemistry·Ahmed DkhissiClaude Pouchan
Nov 13, 2008·Journal of Chemical Theory and Computation·Kevin E RileyKenneth M Merz
Apr 7, 2007·The Journal of Physical Chemistry. a·Tomas KubarPavel Hobza
Aug 11, 2006·The Journal of Physical Chemistry. B·Kevin E Riley, Kenneth M Merz

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