These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Determination of atomic desolvation energies from the structures of crystallized proteins.
    Author: Zhang C, Vasmatzis G, Cornette JL, DeLisi C.
    Journal: J Mol Biol; 1997 Apr 04; 267(3):707-26. PubMed ID: 9126848.
    Abstract:
    We estimated effective atomic contact energies (ACE), the desolvation free energies required to transfer atoms from water to a protein's interior, using an adaptation of a method introduced by S. Miyazawa and R. L. Jernigan. The energies were obtained for 18 different atom types, which were resolved on the basis of the way their properties cluster in the 20 common amino acids. In addition to providing information on atoms at the highest resolution compatible with the amount and quality of data currently available, the method itself has several new features, including its reference state, the random crystal structure, which removes compositional bias, and a scaling factor that makes contact energies quantitatively comparable with experimentally measured energies. The high level of resolution, the explicit accounting of the local properties of protein interiors during determination of the energies, and the very high computational efficiency with which they can be assigned during any computation, should make the results presented here widely applicable. First we used ACE to calculate the free energies of transferring side-chains from protein interior into water. A comparison of the results thus obtained with the measured free energies of transferring side-chains from n-octanol to water, indicates that the magnitude of protein to water transfer free energies for hydrophobic side-chains is larger than that of n-octanol to water transfer free energies. The difference is consistent with observations made by D. Shortle and co-workers, who measured differential free energies of protein unfolding for site-specific mutants in which Ala or Gly was substituted for various hydrophobic side-chains. A direct comparison (calculated versus observed free energy differences) with those experiments finds slopes of 1.15 and 1.13 for Gly and Ala substitutions, respectively. Finally we compared calculated and observed binding free energies of nine protease-inhibitor complexes. This requires a full free energy function, which is created by adding direct electrostatic interactions and an appropriate entropic component to the solvation free energy term. The calculated free energies are typically within 10% of the observed values. Taken collectively, these results suggest that ACE should provide a reasonably accurate and rapidly evaluatable solvation component of free energy, and should thus make accessible a range of docking, design and protein folding calculations that would otherwise be difficult to perform.
    [Abstract] [Full Text] [Related] [New Search]