Journal ArticleDOI
Solvation Energies of Amino Acid Side Chains and Backbone in a Family of Host−Guest Pentapeptides
TLDR
The very large peptide bond ASP, -96 +/- 6 cal/mol/A2, profoundly affects the results of computational comparisons of protein stability which use ASPs derived from octanol-water partitioning data.Abstract:
Octanol-to-water solvation free energies of acetyl amino amides (Ac-X-amides) [Fauchere, J.L., & Pliska, V. (1983) Eur. 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 AcWLm (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 fro 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/A2, 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 flaking 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/A2, profoundly affects the results of computational comparisons of protein stability which use ASPs derived from octanol-water partitioning data.read more
Citations
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Journal ArticleDOI
MEMBRANE PROTEIN FOLDING AND STABILITY: Physical Principles
TL;DR: A coherent thermodynamic formalism for determining and describing the energetics of peptide-bilayer interactions and a review of the properties of the environment of membrane proteins--the bilayer milieu are reviewed.
Journal ArticleDOI
Experimentally determined hydrophobicity scale for proteins at membrane interfaces.
TL;DR: A complete interfacial hydrophobicity scale that includes the contribution of the peptide bond was determined from the partitioning of two series of small model peptides into the interfaces of neutral (zwitterionic) phospholipid membranes.
Journal ArticleDOI
Recognition of transmembrane helices by the endoplasmic reticulum translocon
Tara Hessa,Hyun Kim,Karl Bihlmaier,Karl Bihlmaier,Carolina Lundin,Jorrit Boekel,Helena Andersson,IngMarie Nilsson,Stephen H. White,Gunnar von Heijne +9 more
TL;DR: The results indicate that direct protein–lipid interactions are critical during translocon-mediated membrane insertion, and the basic features of this code are determined, including a ‘biological’ hydrophobicity scale.
Journal ArticleDOI
The principle of gating charge movement in a voltage-dependent K + channel
TL;DR: It is concluded that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore.
Journal ArticleDOI
Molecular code for transmembrane-helix recognition by the Sec61 translocon
Tara Hessa,Nadja M. Meindl-Beinker,Andreas Bernsel,Hyun Kim,Yoko Sato,Mirjam Lerch-Bader,IngMarie Nilsson,Stephen H. White,Gunnar von Heijne +8 more
TL;DR: Using in vitro translation of a model protein in the presence of dog pancreas rough microsomes to analyse a large number of systematically designed hydrophobic segments, a quantitative analysis of the position-dependent contribution of all 20 amino acids to membrane insertion efficiency is presented.
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