Protein Folding And Drug Design

One of the great unsolved problems of science and also physics is the prediction of the three dimensional structure of a protein from its amino acid sequence: the folding problem. It may be stated that the deep connection existing between physics and protein folding is not so much, or in any case not only, through physical methods (experimental: X–rays, NMR, etc, or theoretical: statistical mechanics, spin glasses, etc), but through physical concepts. In fact, protein folding can be viewed as an emergent property not contained neither in the atoms forming the protein nor in the forces acting among them, in a similar way as superconductivity emerges as an unexpected coherent phenomenon taking place on a sea of electrons at low temperature. Already much is known about the protein folding problem, thanks, among other things, to protein engineering experiments as well as from a variety of theoretical inputs: inverse folding problem, funnel–like energy landscapes (Peter Wolynes), helix–coil transitions, etc. Although quite different in appearance, the fact that the variety of models can account for much of the experimental ?ndings is likely due to the fact that they contain much of the same (right) physics. A physics which is related to the important role played by selected highly conserved, “hot”, amino acids which participate to the stability of independent folding units which, upon docking, give rise to a (post–critical) folding nucleus lying beyond the highest maximum of the free energy associated to the process.

This text offers in-depth perspectives on every aspect of protein structure identification, assessment, characterization, and utilization, for a clear understanding of the diversity of protein shapes, variations in protein function, and structure-based drug design. The authors cover numerous high-throughput technologies as well as computational met

One of the great unsolved problems of science and also of physics is the prediction of the three dimensional structure of a protein from its amino acid sequence. It may be stated that the deep connection existing between physics and protein folding is not so much, or in any case not only, through physical methods, but through physical concepts.

This work covers the impact of computational structural biology on protein structure prediction methods, macromolecular function and protein design, and key methods in drug discovery. It also addresses the computational challenges of experimental approaches in structural biology.

A new perspective on the design of molecular therapeutics is emerging. This new strategy emphasizes the rational complementation of functionality along extended patches of a protein surface with the aim of inhibiting protein/protein interactions. The successful development of compounds able to inhibit these interactions offers a unique chance to selectively intervene in a large number of key cellular processes related to human disease. Protein Surface Recognition presents a detailed treatment of this strategy, with topics including: an extended survey of protein-protein interactions that are key players in human disease and biology and the potential for therapeutics derived from this new perspective the fundamental physical issues that surround protein-protein interactions that must be considered when designing ligands for protein surfaces examples of protein surface-small molecule interactions, including treatments of protein-natural product interactions, protein-interface peptides, and rational approaches to protein surface recognition from model to biological systems a survey of techniques that will be integral to the discovery of new small molecule protein surface binders, from high throughput synthesis and screening techniques to in silico and in vitro methods for the discovery of novel protein ligands. Protein Surface Recognition provides an intellectual “tool-kit” for investigators in medicinal and bioorganic chemistry looking to exploit this emerging paradigm in drug discovery.

Helps you choose the right computational tools and techniques to meet your drug design goals Computational Drug Design covers all of the major computational drug design techniques in use today, focusing on the process that pharmaceutical chemists employ to design a new drug molecule. The discussions of which computational tools to use and when and how to use them are all based on typical pharmaceutical industry drug design processes. Following an introduction, the book is divided into three parts: Part One, The Drug Design Process, sets forth a variety of design processes suitable for a number of different drug development scenarios and drug targets. The author demonstrates how computational techniques are typically used during the design process, helping readers choose the best computational tools to meet their goals. Part Two, Computational Tools and Techniques, offers a series of chapters, each one dedicated to a single computational technique. Readers discover the strengths and weaknesses of each technique. Moreover, the book tabulates comparative accuracy studies, giving readers an unbiased comparison of all the available techniques. Part Three, Related Topics, addresses new, emerging, and complementary technologies, including bioinformatics, simulations at the cellular and organ level, synthesis route prediction, proteomics, and prodrug approaches. The book's accompanying CD-ROM, a special feature, offers graphics of the molecular structures and dynamic reactions discussed in the book as well as demos from computational drug design software companies. Computational Drug Design is ideal for both students and professionals in drug design, helping them choose and take full advantage of the best computational tools available. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file.

Peptides serve as effective drugs in the clinic today. However the inherent drawbacks of peptide structures can limit their efficacy as drugs. To overcome this researchers are developing new methods to create ‘tailor-made’ peptides and proteins with improved pharmacological properties. Design of Peptides and Proteins provides an overview of the experimental and computational methods for peptide and protein design, with an emphasis on specific applications for therapeutics and biomedical research. Topics covered include: Computer modeling of peptides and proteins Peptidomimetics Design and synthesis of cyclic peptides Carbohydrates in peptide and protein design De novo design of peptides and proteins Medical development applications An extended case study – the design of insulin variants Design of Peptides and Proteins presents the state-of-the-art of this exciting approach for therapeutics, with contributions from international experts. It is an essential resource for academic and industrial scientists in the fields of peptide and protein drug design, biomedicine, biochemistry, biophysics, molecular modelling, synthetic organic chemistry and medicinal/pharmaceutical chemistry.

One of the great unsolved problems of science and also of physics is the prediction of the three dimensional structure of a protein from its amino acid sequence. It may be stated that the deep connection existing between physics and protein folding is not so much, or in any case not only, through physical methods, but through physical concepts.