Home LiteratureArticle Details
PMID: 8378312 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

What determines the strength of noncovalent association of ligands to proteins in aqueous solution?

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 18 ·1993-09-15 ·Pages 8402-6

Miyamoto S, Kollman PA

Abstract

Free energy perturbation methods using molecular dynamics have been used to calculate the absolute free energy of association of two ligand-protein complexes. The calculations reproduce the significantly more negative free energy of association of biotin to streptavidin, compared to N-L-acetyltryptophanamide/alpha-chymotrypsin. This difference in free energy of association is due to van der Waals/dispersion effects in the nearly ideally performed cavity that streptavidin presents to biotin, which involves four tryptophan residues.

MeSH Terms
Bacterial Proteins/metabolism Biotin/metabolism Calorimetry Chymotrypsin/metabolism Ligands Models, Molecular Protein Binding Protein Conformation Proteins/chemistry,metabolism Streptavidin Tryptophan/analogs & derivatives,metabolism
Chemicals
Bacterial Proteins Ligands Proteins N-acetyltryptophanamide Biotin Tryptophan Streptavidin Chymotrypsin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Miyamoto S
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Kollman P A
References (20)
20 references, click to expand
  1. Energetics of enzyme catalysis.
    Proc Natl Acad Sci U S A. 1978 Nov;75(11):5250-4 PMID: 281676
  2. Calculation of the relative change in binding free energy of a protein-inhibitor complex.
    Science. 1987 Jan 30;235(4788):574-6 PMID: 3810157
  3. Free energy calculations by computer simulation.
    Science. 1987 May 1;236(4801):564-8 PMID: 3576184
  4. Semiquantitative calculations of catalytic free energies in genetically modified enzymes.
    Biochemistry. 1987 May 19;26(10):2669-73 PMID: 3300766
  5. Free energy perturbation calculations on binding and catalysis after mutating Asn 155 in subtilisin.
    Nature. 1987 Aug 6-12;328(6130):551-4 PMID: 3302725
  6. Crystal and molecular structures of the complex of alpha-chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 A resolution.
    J Mol Biol. 1987 May 20;195(2):397-418 PMID: 3477645
  7. Structural origins of high-affinity biotin binding to streptavidin.
    Science. 1989 Jan 6;243(4887):85-8 PMID: 2911722
  8. Hidden thermodynamics of mutant proteins: a molecular dynamics analysis.
    Science. 1989 Jun 2;244(4908):1069-72 PMID: 2727695
  9. Free energy via molecular simulation: applications to chemical and biomolecular systems.
    Annu Rev Biophys Biophys Chem. 1989;18:431-92 PMID: 2660832
  10. A mutant T4 lysozyme (Val 131----Ala) designed to increase thermostability by the reduction of strain within an alpha-helix.
    Proteins. 1990;7(2):198-204 PMID: 2326253
  11. Electrostatic energy and macromolecular function.
    Annu Rev Biophys Biophys Chem. 1991;20:267-98 PMID: 1714279
  12. Construction of new ligand binding sites in proteins of known structure. I. Computer-aided modeling of sites with pre-defined geometry.
    J Mol Biol. 1991 Dec 5;222(3):763-85 PMID: 1749000
  13. A cavity-containing mutant of T4 lysozyme is stabilized by buried benzene.
    Nature. 1992 Jan 23;355(6358):371-3 PMID: 1731252
  14. A molecular dynamics study of thermodynamic and structural aspects of the hydration of cavities in proteins.
    Biopolymers. 1991 Jul;31(8):919-31 PMID: 1782354
  15. Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect.
    Science. 1992 Jan 10;255(5041):178-83 PMID: 1553543
  16. Effect of alanine versus glycine in alpha-helices on protein stability.
    Nature. 1992 Apr 2;356(6368):453-5 PMID: 1557131
  17. Probing protein stability with unnatural amino acids.
    Science. 1992 Jun 26;256(5065):1798-802 PMID: 1615324
  18. Calculations of antibody-antigen interactions: microscopic and semi-microscopic evaluation of the free energies of binding of phosphorylcholine analogs to McPC603.
    Protein Eng. 1992 Apr;5(3):215-28 PMID: 1409541
  19. Stability of a model beta-sheet in water.
    J Mol Biol. 1992 Oct 20;227(4):1244-52 PMID: 1433296
  20. Absolute and relative binding free energy calculations of the interaction of biotin and its analogs with streptavidin using molecular dynamics/free energy perturbation approaches.
    Proteins. 1993 Jul;16(3):226-45 PMID: 8346190
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.18.8402
Published
1993-09-15
Pages
8402-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47364
Subset
IM
Grants
NIGMS NIH HHS · GM-29072 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.18.8402 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2