Molecular recognition in selected biological systems / Liat Shimoni.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Shimoni, Liat.

Contributor:

Glusker, Jenny P., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Biochemistry.

Biochemistry--Penn dissertations.

Penn dissertations--Molecular biophysics.

Molecular biophysics--Penn dissertations.

Biochemistry and Molecular biophysics.

Biochemistry and Molecular Biophysics.

Academic Dissertations as Topic.

Medical Subjects:

Biochemistry and Molecular Biophysics.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Biochemistry.

Biochemistry--Penn dissertations.

Penn dissertations--Molecular biophysics.

Molecular biophysics--Penn dissertations.

Biochemistry and Molecular biophysics.

Physical Description:

xii, 123 pages : illustrations ; 29 cm

Production:

1998.

Summary:

The focus of this work is the analysis of molecular recognition in selected biological systems. Geometrical parameters and graph-set analysis of molecular interactions were evaluated from molecular structure of proteins and small molecules determined by X-ray diffraction methods. The energetic aspects of the studied systems we evaluated using ab initio molecular orbital calculations. Hydrogen bonding between a donor, D-H, and an acceptor, A, were inspected in a variety of systems. One system involves the acceptor atoms 0 and/or N, in protein-protein, protein-nucleic acid, or basepair hydrogen bonding interactions, and the second involves the acceptor atom fluorine, common in drug-enzyme binding recognition. Molecular interactions involving the metal ions lead and copper were also analyzed; electronic configurations and effects on metalligand interactions, as well as geometrical consequences of relativistic effects on Pb(II) complexes, and the Jahn Teller effect on Cu(II) complexes, were studied. In addition, the secondary and quaternary structure of the enzyme porphobilinogen synthase were predicted based on preliminary X-ray results. Graph-set analysis showed that the bidentate hydrogen bonding pattern in protein-protein and base-pair recognition is R2 2(8) while that in protein DNA recognition is R2 2(9). The D-H...F interaction, although weaker than D-H ...O(N), is found to contribute to molecular alignment in the crystalline state, especially when several such interactions are present. It was also found that the fluorine atom tends to form contacts with C-H protons, where as O and/or N atoms tend to bind to the more acidic protons (O-H, N-H). The binding recognition of Pb(II) was shown to be either spherical or hemi-spherical; depending on the stereoactivity of the lone pair of electrons, the coordination number and the liganding atoms. The results have shown that geometrical differences between corresponding Cu(I) and Cu(II) complexes depends on specific ligand combinations, and can affect the functionality of the copper site. Type I copper enzymes were found to have similar geometrical parameters in the corresponding Cu(I) and Cu(II) centers. Porphobilinogen synthase was predicted to have a TIM barrel folding pattern. The proposed enzyme packing mode involved a non-crystallographic rotation axis of the two molecules in the asymmetric unit, and is consistent with earlier studies.

Notes:

Supervisor: Jenny P. Glusker.

Thesis (Ph.D. in Biochemistry and Molecular biophysics) -- University of Pennsylvania, 1998.

Includes bibliographical references and index.

Local Notes:

University Microfilms order no.: 99-13520.

OCLC:

187478191