Protein Allostery in Drug Discovery (Advances in Experimental Medicine and Biology Book 1163)

The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery--as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc. Front Matter ....Pages i-xii Allostery in Drug Development (Xi Cheng, Hualiang Jiang)....Pages 1-23 Dynamic Protein Allosteric Regulation and Disease (Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang)....Pages 25-43 Protein Allostery in Rational Drug Design (Takayoshi Kinoshita)....Pages 45-64 Progress in Allosteric Database (Kun Song, Jian Zhang, Shaoyong Lu)....Pages 65-87 Correlation Between Allosteric and Orthosteric Sites (Weilin Zhang, Juan Xie, Luhua Lai)....Pages 89-105 Characteristics of Allosteric Proteins, Sites, and Modulators (Xinheng He, Duan Ni, Shaoyong Lu, Jian Zhang)....Pages 107-139 Advances in the Computational Identification of Allosteric Sites and Pathways in Proteins (Xavier Daura)....Pages 141-169 Advances in NMR Methods to Identify Allosteric Sites and Allosteric Ligands (Hazem Abdelkarim, Ben Hitchinson, Avik Banerjee, Vadim Gaponenko)....Pages 171-186 Interrogating Regulatory Mechanisms in Signaling Proteins by Allosteric Inhibitors and Activators: A Dynamic View Through the Lens of Residue Interaction Networks (Lindy Astl, Amanda Tse, Gennady M. Verkhivker)....Pages 187-223 GPCR Allosteric Modulator Discovery (Yiran Wu, Jiahui Tong, Kang Ding, Qingtong Zhou, Suwen Zhao)....Pages 225-251 Allosteric Small-Molecule Serine/Threonine Kinase Inhibitors (Resmi C. Panicker, Souvik Chattopadhaya, Anthony G. Coyne, Rajavel Srinivasan)....Pages 253-278 Allosteric Regulation of Protein Kinases Downstream of PI3-Kinase Signalling (Alejandro E. Leroux, Lissy Z. F. Gross, Mariana Sacerdoti, Ricardo M. Biondi)....Pages 279-311 Allosteric Modulators of Protein–Protein Interactions (PPIs) (Duan Ni, Na Liu, Chunquan Sheng)....Pages 313-334 Allosteric Modulation of Intrinsically Disordered Proteins (Ashfaq Ur Rehman, Mueed Ur Rahman, Taaha Arshad, Hai-Feng Chen)....Pages 335-357 Engineering Allostery into Proteins (Scott D. Gorman, Rebecca N. D’Amico, Dennis S. Winston, David D. Boehr)....Pages 359-384