Molecular Recognition in Pharmacology

This unique volume gives the basics of thermodynamics and kinetics of complex formation between ligands and receptors. The book is intended for pharmacologists, chemists, physics engaged in the creation of new medicinal substances.

This unique volume traces the behavior of the drug substance, starting from the initial pre-contact stage, and ending with the formation of the complex. Molecular recognition lies in the foundation of every life form and includes many mysteries. Currently, studies on this topic in pharmacology are limited to determining the properties of complexes of medicinal substances (drugs) with specific (complementary) biomolecules: receptors, enzymes, ion channels etc. The results present the mechanisms preventing drugs from such non-specific binding. This direction is very fruitful, although the phenomenon of molecular recognition is far wider.

Features

• Presents the basics of thermodynamics and kinetics of complex formation between ligands and receptors
• Selected novel therapeutic concepts are tested and validated
• Provides a review of the pharmacophore approach and drug design methods
• By its nature, pharmacology is a multi-disciplinary science, hence, disciplinary areas include chemistry, biology and neuroscience

• Discusses hot topics including 3D structure determination techniques and in silico methods and neural networks The main theme of the book is the consideration of mechanisms created by nature to protect physiologically active substances from being stuck on nonspecific acceptors in the body. The book describes the materials that aid in the development of new medicinal substances. It is intended for researchers, as well as upper-level undergraduate and graduate students interested in the problems of molecular pharmacology and drug design.

  Autorentext

  Mikhail Borisovich Darkhovskiy graduated from Moscow State University in 1996 with a major in Quantum Chemistry. In 2005 he earned a PhD in Chemistry and Solid-State Physics under the supervision of Dr. Andrei Thougreeff. His research was in electronic structure and transformation of spin- isomers of iron and cobalt complexes in spin transitions using the QM/ MM effective crystal field method. Together with Professor Dukhovich, he investigated the factors involved in molecular recognition in "ligand-receptor" systems, the influence of water on complex strength, and conformational entropy as a hidden factor for complex formation. Currently, he works in the biotech startup InterX (a subsidiary of NeoTX company), participating in the development of methods for the accurate prediction of compounds' binding affinity to proteins. His awards include the INTAS Young Scientist award, and, Emory University Visiting Scientist award (Cherry L. Emerson Center for Scientific Computation Fellowship).

  Inhalt

  Chapter 1 Energy of Intermolecular Interactions in Drug-Receptor Complex Formation

Chapter 2 Methods for Studying Drug-Receptor Binding

Chapter 3 Methods for Drug Discovery Research

Chapter 4 Thermodynamics of Drug-Receptor Complex Formation

Chapter 5 Effect of conformation entropy on affinity of specific ligands

Chapter 6 Kinetics of Drug-Receptor Complex Formation

Chapter 7 Distant and Contact Interactions of Drugs with Specific and Non-specific Receptors

Chapter 8 Influence of bound water on interaction of the chemical groups in drugs and receptors

Chapter 9 Information Required for Receptor Recognition

Chapter 10 Agonists and Antagonists

Chapter 11. Non-selective Drugs

Chapter 12 Search Paths for Novel Therapeutics