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)- Click here for the pdf) (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.

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

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

9.              Google Search

10.           Google Search with thiol OR sulfhydryl

11.           Yahoo

12.           MSN

13.           Altavista

14.           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

Internet articles:

1. The Anemone and the Balance. The Chemweb Preprint Server 2003. html or pdf.
2. 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 or MS Word  (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 or Simple_Balance_PartI.doc or SBPI.ppt

b.     Simple_Balance_PartII.pdf or Simple_Balance_PartII.doc or SBPII.ppt

c.     Balance_Gedanken_Experiment.pdf or Gedanken_Experiment.doc or SBGE.ppt

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. Altavista
5. Google Book Search
6. Amazon.com

Receptor Desensitization Searches:

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

Receptor Modulation Searches:

1. Google
2. Yahoo
3. MSN
4. Altavista
5. 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, Molecular Recognition, Drug Action, GPCR activation, Efficacy, Redox-active Cysteine, Structural Biology, GPCR, Cysteine Modulation, Receptor Activation, Pharmacological Theory, Electrostatic Switch, Pharmaceutical Science, Computational Models, Signal Transduction, Mathematical Models, Biotechnology, Molecular Modeling, Drug Discovery, 7TMR, Molecular Pharmacology, B2AR, Thiol, Sulfhydryl Group Modulation, Receptor Activation Mechanism, Response Trigger, Receptor Models, Electrostatic Molecular Models, Biological Simulation, Drug-Receptor Response, Molecular Mechanism for Beta-Adrenergic Receptor Activation, Redox Modulation, Allosteric, Activation of  Receptors, Ligand Binding

Thiol-based systems involved in the maintenance of the cellular redox balance. Thiol-disulfide balance: from the concept of oxidative stress to that of redox regulation. Antioxid Redox Signal, Thiol/disulfide, protean agonism, allosteric modulation, How do receptors work? GPCR activation, Mechanism of receptor activation, G protein-coupled receptors, 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, possible new drug therapies for improving the current treatment for heart failure, asthma, COPD and Parkinson’Äôs disease by preventing drug tolerance, desensitization or wearing-off. How do receptors transmit signals

Key Words: Biotechnology, Pharmacology, Molecular Recognition, Signal Transduction, Redox-active Cysteine, GPCRs, 7TMR, Allosteric, Cysteine, Thiol, Sulfhydryl, Redox, Molecular Modeling, Drug Discovery, Structural Biology, Molecular Pharmacology, Efficacy, Receptor Response Theory, Pharmaceutical Science, Computational Models, Mathematical Models, Activation of  Receptors, GPCR activation, How do receptors work? Mechanism of receptor activation, G protein-coupled receptors, 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, beta-adrenergic receptors, we love drug receptor modeling

Key Words: Pharmacology, Innovation generation, Agonist/antagonist combinations, A mechanistic interpretation of receptor activation, Biophysics, Cysteine, Thiol, Sulfhydryl, Redox, Efficacy, Receptor Response Theory, Pharmaceutical Science, Computational Models, Mathematical Models, Activation of  Receptors, GPCR activation, Allosteric, How do receptors work?, Molecular Recognition, GPCRs, 7TMR, Molecular Modeling, Mechanism of receptor activation, G protein-coupled receptors, 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.