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| Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides |
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| Author(s): Wimley WC, Creamer TP, White SH |
| Source: BIOCHEMISTRY Volume: 35 Issue: 16 Pages: 5109-5124 Published: APR 23 1996 |
| Times Cited: 204 References: 57 |
| Abstract: Octanol-to-water solvation free energies of acetyl amino acid amides (Ac-X-amides) [Fauchere, J. L., & Pliska, V. (1983) fur. J. Med. Chem.-Chim. Ther. 18, 369] form the basis for computational comparisons of protein stabilities by means of the atomic solvation parameter formalism of Eisenberg and McLachlan [(1986) Nature 319, 199]. In order to explore this approach for more complex systems, we have determined by octanol-to-water partitioning the solvation energies of (1) the guest (X) side chains in the host-guest pentapeptides AcWL-X-LL, (2) the carboxy terminus of the pentapeptides, and (3) the peptide bonds of the homologous series of peptides AcWL(m) (m = 1-6). Solvation parameters were derived from the solvation energies using estimates of the solvent-accessible surface areas (ASA) obtained from hard-sphere Monte Carlo simulations. The measurements lead to a side chain solvation-energy scale for the pentapeptides and suggest the need for modifying the Asp, Glu, and Cys values of the ''Fauchere-Pliska'' solvation-energy scale for the Ac-X-amides. We find that the unfavorable solvation energy of nonpolar residues can be calculated accurately by a solvation parameter of 22.8 +/- 0.8 cal/mol/A(2), which agrees satisfactorily with the Ac-X-amide data and thereby validates the Monte Carlo ASA results. Unlike the Ac-X-amide data, the apparent solvation energies of the uncharged polar residues are also largely unfavorable. This unexpected finding probably results, primarily, from differences in conformation and hydrogen bonding in octanol and buffer but may also be due to the additional flanking peptide bonds of the pentapeptides. The atomic solvation parameter (ASP) for the peptide bond is comparable to the ASP of the charged carboxy terminus which is an order of magnitude larger than the ASP of the uncharged polar side chains of the Ac-X-amides. The very large peptide bond ASP, -96 +/- 6 cal/mol/Angstrom(2), profoundly affects the results of computational comparisons of protein stability which use ASPs derived from octanol-water partitioning data. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF IRVINE, DEPT PHYSIOL & BIOPHYS, IRVINE, CA 92717 USA
2. JOHNS HOPKINS UNIV, SCH MED, DEPT BIOPHYS & BIOPHYS CHEM, BALTIMORE, MD 21205 USA |
| Publisher: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: UG547 |
| ISSN: 0006-2960 |
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