Bio Balance - Reference Library

 

Articles and papers:

1. Molecular dynamics of a biophysical model for beta-2-adrenergic and G protein-coupled receptor activation Journal of Molecular Graphics and Modelling 25: 396-409 (2006). For a picture of this model - Click here
2. Optimal Agonist/Antagonist Combinations Maintain Receptor Response by Preventing Rapid Beta-1 adrenergic Receptor Desensitization Intl. J. Pharmacol., 1(2): 122-131, 2005. pdf.
3. Activation of G Protein-Coupled Receptors Entails Cysteine Modulation of Agonist Binding, J. Molecular Structure (Theochem), 430/1-3: 57-71 (1998). pdf .
4. Weber's Law Modeled by the Mathematical Description of a Beam Balance, Mathematical Biosciences 122: 89-94 (1994). pdf .
5. Compositions to enhance the safety and efficacy of bio-pharmaceutical drugs. USP 6,593,094; 2003 link.
6. Drug compositions to prevent desensitization of cellular receptors. USP 6,673,558; 2004 link.

Enhanced Pharmaceuticals

Evidence for a free sulfhydryl or thiol group involved with receptor activation (A mechanistic hypothesis of receptor function involving sulfhydryl modulation and redox regulation):

1. Google Search
2. Yahoo Search
3. MSN Search
4. S-nitrosoglutathione inhibits {alpha}1-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery
5. EXTRACELLULAR THIOLS AND THIOL/DISULFIDE REDOX IN METABOLISM
6. Synaptic Cysteine Sulfhydryl Groups as Targets of Electrophilic Neurotoxicants
7. S-Nitrosothiols modulate G protein-coupled receptor signaling in a reversible and highly receptor-specific manner
8. Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270
9.  Inactivation of the Purified Bovine mu Opioid Receptor by Sulfhydryl Reagents
10. Importance of thiol groups in ligand binding to D2 dopamine receptors from brain and anterior pituitary gland
11. S-Nitrosylation Signaling in Cell Biology
12. The 'allosteric modulator' SCH-202676 disrupts G protein-coupled receptor function via sulphydryl-sensitive mechanisms
13. Evidence that non-covalent forces, thiol and disulphide groups affect the structure and binding properties of the prolactin receptor on hepatocytes from pregnant rats
14. Nitric oxide directly activates GABA(A) receptor function through a cGMP/protein kinase-independent pathway in frog pituitary melanotrophs
15. Receptor-Induced Thiolate Couples Env Activation to Retrovirus Fusion and Infection
16. The Chemistry of Olfactory Reception: Stimulus-Specific Protection from Sulfhydryl Reagent Inhibition
17. Versatility and Differential Roles of Cysteine Residues in Human Prostacyclin Receptor Structure and Function
18. Pharmacologic Receptor Activity of Rabbit Aorta
19. Exploiting Thiol Modifications
20. Reactivity of free thiol groups in type-I inositol trisphosphate receptors
21. Cysteine regulation of protein function as exemplified by NMDA-receptor modulation
22. Potentiation in various agonists-induced contractions of rabbit mesenteric artery by sulfhydryl reagents
23. Reduced sulfhydryl groups are required for activation of uterine progesterone receptor. Possible involvement of an inhibitor of activation
24. Regulation of opioid receptor binding; Possible mechanisms of sulfhydryl groups in the binding site
25. Inactivation of the Purified Bovine mu-Opioid Receptor by Sulfhydryl Reagents
26. Balancing reactivity against selectivity: The evolution of protein S-nitrosylation as an effector of cell signaling by nitric oxide
27. Selective enhancement of histamine H1-receptor responses in guinea-pig ileal smooth muscle by 1,4-dithiothreitol
28. 1,4-Dithiothreitol-induced changes in histamine H1-agonist efficacy and affinity in the longitudinal smooth muscle of guinea-pig ileum
29. The Agonist Binding Site on the Bovine Bradykinin B2 Receptor Is Adjacent to a Sulfhydryl and Is Differentiated from the Antagonist Binding Site by Chemical Cross-linking

Evidence for redox modulation of the receptor response:

1.              Reducing and Oxidizing Agents Sensitize Heat-Activated Vanilloid Receptor (TRPV1) Current

2.              Google Search (receptor response)

3.              Google Search (signal transduction)

4.              Redox Receptor Regulation Revealed

5.              Hypoxia Enhances S-Nitrosylation-Mediated NMDA Receptor Inhibition via a Thiol Oxygen Sensor Motif

6.              Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control

7.              Cell Growth and Thiols

8.              Free Radicals in the Physiological Control of Cell Function

Evidence for an electrostatic mechanism for receptor-ligand interactions:

1.     Google Search

2.     Google Search with thiol OR sulfhydryl

3.     Yahoo

4.     MSN

5.     Unifying Electrostatic Mechanism for Receptor-Ligand Activity

Evidence for the role of the disulfide bond in receptor function:

1.              Role of extracellular disulfide-bonded cysteines in the ligand binding function of the beta 2-adrenergic receptor

2.              Pubmed Search

3.              The high affinity state of the beta 2-adrenergic receptor requires unique interaction between conserved and non-conserved extracellular loop cysteines

4.              Google

5.              Yahoo

6.              Role of cysteine residues of rat A2a adenosine receptors in agonist binding

7.              Roles of sulfhydryl and disulfide groups in the binding of CP-55,940 to rat brain cannabinoid receptor

8.              The human growth hormone (GH) receptor and its truncated isoform: sulfhydryl group inactivation in the study of receptor internalization and GH-binding protein generation

9.              Role of disulfides and sulfhydryl groups in agonist and antagonist binding in serotonin1A receptors from bovine hippocampus

***How Receptors Work? ***

Internet articles:

1. The Devilish Complexity of Cysteine Modulation in Protein Function (2008).
2. My Blog (2008 - 2010).
3. Helium (2008 - 2009).
4. The Anemone and the Balance. The Chemweb Preprint Server 2003. html or pdf.
5. Desensitization of a balance with Langmuir binding of weights. arXiv 2003, http://arXiv.org/abs/physics/0303055. html or pdf.

Wikipedia articles:

1.              Weber's law

2.              G Protein-Coupled Receptors (GPCRs)

3.              Adrenergic receptors

4.              Nanotechnologies

Scholarpedia articles:

Stability of Equilibria

Appendix and Graphics:

1. Electrostatic Plots of the Two-States of the Beta-2-Adrenergic Receptor
2. Explore a receptor on a cell
3. Free Pics of Electrostatic Potential Plots
4. Graphics SECTION
5. 5HT or serotonin receptor models
6. APPENDIX2 - Diagram of Receptor Activation MS Word, or html
7. APPENDIX SECTION - Derivation of the Method  MS Word, or html

Essays:

1.  Receptor Structure to Function (2008)
2.  The Scientific Rationale for Improving Drugs (2006).
3.  "A Question of Balance? Nonlinear Complex Phenomena in Biology and Physics" (2006).
4. "The FDA Role in Drug Safety" (2005).
5. "Why Aren't Drugs Safer? - Is It Because We Need A Fundamental Understanding of the Receptor Response?" (2005).
6. "A Possible Mechanism for the "Broken Heart" Syndrome" html or MS Word (2005).
7. "New Agonist/Antagonist Optimal Ratio Combinations as a Potentially Safer Class of Pharmaceutical Drugs" html or MS Word (2005).
8. "The Overlooked Problem of Drug-Receptor Desensitization" html or MS Word (2005).
9. "Advancing in the face of conventional wisdom" Drug Discovery Today (www.drugdiscoverytoday.com) Vol. 9, February 2004 pdf  (2004).
10. Essay - The role of drug-receptor desensitization (tolerance, fade, tachyphylaxis or down-regulation) for future drug development html (2004).
11. Essay - Better drugs without genetic testing? html or MS Word (2004).

Free Software:

Prototype Download Page

Science Fair Projects (with a simple two-pan balance a student could use the following articles for an interesting project):

1. An introduction to the surprising complexities of the simple two-pan balance revealed here (in Adobe pdf, Microsoft Word or PowerPoint format):

a.     Simple_Balance_PartI.pdf

b.     Simple_Balance_PartII.pdf

c.     Balance_Gedanken_Experiment.pdf 

2. Weber's Law Modeled by the Mathematical Description of a Beam Balance, Mathematical Biosciences 122: 89-94 (1994). pdf .
3. Desensitization of a balance with Langmuir binding of weights. arXiv 2003, http://arXiv.org/abs/physics/0303055. html or pdf.
4. The Anemone and the Balance. The Chemweb Preprint Server 2003. html or pdf.

Health Alerts:

Health Alerts - as a service to the community

Receptor Activation Searches:

1. Google
2. Yahoo
3. MSN
4. Google Book Search
5. Amazon.com

Receptor Desensitization Searches:

1. Google
2. Yahoo
3. MSN
4. Google Book Search

Receptor Modulation Searches:

1. Google
2. Yahoo
3. MSN
4. Google Book Search

Arguments, crazy ideas and open communication are the lifeblood of science.

A balance that does not tremble cannot weigh.

 A man who does not tremble cannot live.

 - Erwin Chargaff

Key Words: Pharmacology, Agonist/antagonist combinations, GPCR structure, Biophysics, Cysteine, Thiol, Sulfhydryl, Redox, Efficacy, Receptor Response Theory, Pharmaceutical Science, Computational Models, Mathematical Models, Activation of  Receptors, GPCR activation, Enhanced Pharmaceuticals, Allosteric, How do receptors work?, Molecular Recognition, GPCRs, 7TMR, Molecular Modeling, Mechanism of receptor activation, G protein-coupled receptors, A mechanistic interpretation of receptor activation, G-protein-coupled receptors, G protein coupled receptors, molecular mechanism for the receptor response, molecular mechanism of the receptor response, molecular mechanism of signal transduction, How do drug receptors work?, 5-HT2A, serotonin, Biotechnology, beta-adrenergic receptors, we love drug receptor modeling, Antioxid Redox Signal, Webers law, Weber-Fechner law,  Balance, Equilibrium, two-state model, acid-base model, Redox-active Cysteine, Net shift in receptor states, Signal Transduction, Drug Discovery, Structural Biology, Molecular Pharmacology.