Chem Asian J 2015 Apr 5;10(4):1071-8. Epub 2015 Mar 5.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
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J Org Chem 2002 Mar;67(6):1827-37
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143, USA.
We have used a newly developed qualitative computational approach, PROFEC (Pictorial Representation of Free Energy Changes), to visualize the areas of the ligand biotin where modifications of its structure might lead to tighter binding to the protein streptavidin. The PROFEC analysis, which includes protein flexibility and ligand solvation/desolvation, led to the suggestion that the pro-9R hydrogen atom of biotin, which is in alpha-position to the CO(2)(-) group, might be changed to a larger group and lead to better binding with streptavidin and avidin. Free energy calculations supported this suggestion and predicted that the methyl analogue should bind approximately 3 kcal/mol more tightly to streptavidin, with this difference coming exclusively from the relative desolvation free energy of the ligand. Read More
J Phys Chem B 2009 Jul;113(29):9958-67
National Institute for Nanotechnology, 11421 Saskatchewan Drive, Edmonton, Alberta, T6G 2M9, Canada.
We studied the electronic structure of the binding site of the streptavidin-biotin complex by using the ONIOM method at the HF/STO-3G:UFF level and obtained the solvation structure of the complex by using the statistical-mechanical, three-dimensional molecular theory of solvation (aka three-dimensional reference interaction site model, 3D-RISM-KH). All the streptavidin residues located within 3 A of the biotin residue were included in the quantum mechanical (QM) layer. In total, 16 residues including biotin with 274 atoms were in the QM layer, in which five residues are responsible for the hydrophobic interactions and nine residues for the hydrogen-bonding/electrostatic interaction with biotin. Read More
J Am Chem Soc 2007 May 7;129(17):5419-29. Epub 2007 Apr 7.
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
The unusually strong reversible binding of biotin by avidin and streptavidin has been investigated by density functional and MP2 ab initio quantum mechanical methods. The solvation of biotin by water has also been studied through QM/MM/MC calculations. The ureido moiety of biotin in the bound state hydrogen bonds to five residues, three to the carbonyl oxygen and one for each--NH group. Read More
Bioorg Med Chem 2014 Oct 24;22(19):5476-86. Epub 2014 Jul 24.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address:
The pathway of ligand dissociation and how binding sites respond to force are not well understood for any macromolecule. Force effects on biological receptors have been studied through simulation or force spectroscopy, but not by high resolution structural experiments. To investigate this challenge, we took advantage of the extreme stability of the streptavidin-biotin interaction, a paradigm for understanding non-covalent binding as well as a ubiquitous research tool. Read More