HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lomize, A. L. Articles by Pogozheva, I. D. Search for Related Content PubMed PubMed Citation Articles by Lomize, A. L. Articles by Pogozheva, I. D. Social Bookmarking                   What's this?

Interatomic potentials and solvation parameters from protein engineering data for buried residues

College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, USA

Reprint requests to: Andrei L. Lomize, College of Pharmacy University of Michigan, 428 Church St., Ann Arbor, MI 48109-1065; e-mail: almz{at}umich.edu; fax: 734-763-5595.

Van der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (H-bonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of free-energy differences. The set of mutants included substitutions of uncharged, inflexible, water-inaccessible residues in -helices and ß-sheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and H-bonds were smaller than in molecular mechanics and followed the "like dissolves like" rule, as expected in condensed media but not in vacuum. The depths of modified Lennard-Jones potentials were -0.34, -0.12, and -0.06 kcal/mole for similar atom types (polar–polar, aromatic–aromatic, and aliphatic–aliphatic interactions, respectively) and -0.10, -0.08, -0.06, -0.02, and nearly 0 kcal/mole for different types (sulfur–polar, sulfur–aromatic, sulfur–aliphatic, aliphatic–aromatic, and carbon–polar, respectively), whereas the depths of H-bond potentials were -1.5 to -1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, -1, -21, and -66 cal/moleŲ for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the water–protein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.

Keywords: Free energy; protein engineering; solvation; energy functions; protein stability; secondary structure; protein folding

Abbreviations: vdW, van der Waals • ASA, accessible surface areas • ASP, atomic solvation parameter • PDB, Protein Data Bank, H-bond, hydrogen bond, BPTI, bovine pancreatic trypsin inhibitor • r.m.s.d., root mean square deviation

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Santos, V. A. Risso, M. P. Sica, and M. R. Ermacora Effects of Serine-to-Cysteine Mutations on {beta}-Lactamase Folding Biophys. J., September 1, 2007; 93(5): 1707 - 1718. [Abstract] [Full Text] [PDF]

				A. L. Lomize, I.D. Pogozheva, and H.I. Mosberg Quantification of helix-helix binding affinities in micelles and lipid bilayers Protein Sci., October 22, 2004; 13(10): 2600 - 2612. [Abstract] [Full Text] [PDF]

				M. Petukhov, G. Rychkov, L. Firsov, and L. Serrano H-bonding in protein hydration revisited Protein Sci., August 1, 2004; 13(8): 2120 - 2129. [Abstract] [Full Text] [PDF]

				A. Bhaduri, G. Pugalenthi, N. Gupta, and R. Sowdhamini iMOT: an interactive package for the selection of spatially interacting motifs Nucleic Acids Res., July 1, 2004; 32(suppl_2): W602 - W605. [Abstract] [Full Text] [PDF]

				G.-Y. Li and J. L. Koenig FTIR Mapping: Polymer Swelling and Solvent Segregation in Benzene/Cyclohexane-Polyisoprene Rubber System Journal of Elastomers and Plastics, January 1, 2004; 36(1): 33 - 44. [Abstract] [PDF]

				K. Takano, J. M. Scholtz, J. C. Sacchettini, and C. N. Pace The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent J. Biol. Chem., August 22, 2003; 278(34): 31790 - 31795. [Abstract] [Full Text] [PDF]

				A. Anishkin, V. Gendel, N. A. Sharifi, C.-S. Chiang, L. Shirinian, H. R. Guy, and S. Sukharev On the Conformation of the COOH-terminal Domain of the Large Mechanosensitive Channel MscL J. Gen. Physiol., February 24, 2003; 121(3): 227 - 244. [Abstract] [Full Text] [PDF]