1. Biophysical Approaches
Biophysical Approaches to Drug Design
Overall Organization of the Topic
Approaches Useful in Drug Design
Fluorescence Spectroscopy
- Principle of Fluorescence
- Factors governing fluorescence intensity
- Fluorescent groups
- Sensitivity of Fluorescence to Environment
- Fluorescence Resonance Energy Transfer
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Biophysical Approaches

2. Biophysical Approaches
Biophysical Approaches Useful in Drug Design
Absorption Spectroscopy
Fluorescence Spectroscopy
Infrared Spectroscopy
Raman Spectroscopy
Nuclear Magnetic Resonance Spectroscopy
Electron Spin Resonance Spectroscopy
Circular Dichroism
Centrifugation Techniques
X-ray Crystallography
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Biophysical Approaches

3. Biophysical Approaches
Fluorescence Spectroscopy
Principle
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Biophysical Approaches

4. Biophysical Approaches
Electronic States of Molecules
Example of Ethylene
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Biophysical Approaches

5. Biophysical Approaches
Obtaining Fluorescence Spectrum
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Biophysical Approaches

6. Biophysical Approaches
Factors Governing Fluorescence Intensity
Internal Conversion (kIC)
Collisional De-excitation (kQ)
Intersystem Crossing (kIS)
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Biophysical Approaches

7. Biophysical Approaches
Fluorescent Groups
Intrinsic Groups in Proteins and Nucleic Acids
- Trp, Tyr, Phe, Cys, Adenine, Guanine, … _ +
Tryptophan Tyrosine Phenylalanine Cysteine
Adenosine Guanosine
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Biophysical Approaches

8. Biophysical Approaches
Fluorescent Groups
External Probes
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Biophysical Approaches

9. Biophysical Approaches
Sensitivity of Fluorescence to Environment
Determination of Equilibrium Dissociation Constants
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Biophysical Approaches

10. Biophysical Approaches
Binding Affinities as a Function of Structure
Varying the Receptor
Mutant KD DGO
(nM) (kcal/mol) WT
R47H
R129H
K125M
K114A ,
Varying the Ligand
Ligand KD DGO
(nM) (kcal/mol)
DEFGH’ ~1×
DEFGH ~1×
DEFG
DEF ,
EFGH ,
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Biophysical Approaches

11. Biophysical Approaches
Fluorescence Resonance Energy Transfer
Principle
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Biophysical Approaches

12. Biophysical Approaches
Fluorescence Resonance Energy Transfer
Determining Substrate Specificities
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Biophysical Approaches