Abstract

Dissection of the different entropic contributions for proteins is still incomplete due to the fact that most of the terms that contribute to it are strongly correlated to one another as well as to some enthalpic contributions. In a previous paper (Proteins25:146-156), we estimated the magnitude of backbone entropy associated with the folding-unfolding transition. Nevertheless, this contribution itself is not sufficient to predict accurately the unfolding endotherm for a globular protein. In our present calculations, the error of conformational entropy is less than 3% but such a difference could account for as much as q 10 C in the stability of an average globular protein. This project aims to dissect the effect of electrostatic charges to the backbone entropy. Several dipeptides containing different combinations of charges and distances in between them were generated using Quanta and their energies were calculated and minimized using fixed dihedrals in Xplor and the OPLS parameters. These backbone entropy values reflect a change that could account for some of the difference between the calculated and the experimental stability for globular proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR004328-10
Application #
6122026
Study Section
Project Start
1997-08-05
Project End
1998-08-04
Budget Start
Budget End
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Jaganaman, Sunil; Pinto, Alex; Tarasev, Michael et al. (2007) High levels of expression of the iron-sulfur proteins phthalate dioxygenase and phthalate dioxygenase reductase in Escherichia coli. Protein Expr Purif 52:273-9
Todd, M J; Gomez, J (2001) Enzyme kinetics determined using calorimetry: a general assay for enzyme activity? Anal Biochem 296:179-87
Karantza, V; Freire, E; Moudrianakis, E N (2001) Thermodynamic studies of the core histones: stability of the octamer subunits is not altered by removal of their terminal domains. Biochemistry 40:13114-23
Griko, Y V; Remeta, D P (1999) Energetics of solvent and ligand-induced conformational changes in alpha-lactalbumin. Protein Sci 8:554-61
Lee, R T; Gabius, H J; Lee, Y C (1998) Thermodynamic parameters of the interaction of Urtica dioica agglutinin with N-acetylglucosamine and its oligomers. Glycoconj J 15:649-55
Zakharov, S D; Lindeberg, M; Griko, Y et al. (1998) Membrane-bound state of the colicin E1 channel domain as an extended two-dimensional helical array. Proc Natl Acad Sci U S A 95:4282-7
Luque, I; Todd, M J; Gomez, J et al. (1998) Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis. Biochemistry 37:5791-7
Chu, V; Freitag, S; Le Trong, I et al. (1998) Thermodynamic and structural consequences of flexible loop deletion by circular permutation in the streptavidin-biotin system. Protein Sci 7:848-59
Luque, I; Freire, E (1998) Structure-based prediction of binding affinities and molecular design of peptide ligands. Methods Enzymol 295:100-27
Luque, I; Gomez, J; Semo, N et al. (1998) Structure-based thermodynamic design of peptide ligands: application to peptide inhibitors of the aspartic protease endothiapepsin. Proteins 30:74-85

Showing the most recent 10 out of 86 publications