A novel knowledge-based computational antibody design methodology an application have been developed for the design of antibodies and antibody therapeutics to targets of interest. It has been rigorously benchmarked to reproduce native antibody structures and sequences, and has been used to successfully design an antibody to a target antigen as a proof of concept of de novo design. Our lab’s recent clustering of the structures of antibody Complementary Determining Regions (CDRs) in the Protein Data Bank (PDB) enabled the development of the antibody analysis software and database, PyIgClassify, which forms the core of this knowledge-based approach where we use the structural clusters and associated sequence profiles to guide design. The Program uses the Rosetta energy function and new methods for reliable CDR grafting, cluster-based constraints, profile-based sequence design, and flexible-backbone design to computationally test hundreds of thousands of prospective antibody designs in the span of days. Methods were developed for quickly analyzing structural properties of potential designs using the Rosetta FeatureReporter framework, while a Graphical User Interface (GUI), PyIgDesign, was created to aid in antibody design selection. The Rosetta Antibody Design (RAbD) program is meant to sample the diverse sequence, structure, and binding space of an antibody to an antigen. It was developed to enable near-complete customization for a variety of design strategies and projects and can design antibodies for a broad range of applications, from affinity of existing antibody-antigen complex structures to de novo design in which whole new sequences and antibody-antigen contacts are created.

This book compiles updated research about the implications of therapeutic proteins in various human diseases. The initial chapters of the book provide basic information on the therapeutic proteins and discuss techniques for their formulation, production, and analytic approaches for their characterization. The subsequent chapters shed light on therapies based on therapeutic proteins against metabolic disorders, neurological disorders, cancer, autoimmune disorders, and infectious diseases. Importantly, it presents the factors influencing the immunogenicity of therapeutic proteins, including, genetic factors, disease type, and origin of therapeutic protein, dose frequency, administration route, and treatment duration. The book also reviews the strategies for reducing immunogenicity associated with therapeutic proteins, including PEGylation, site specific mutagenesis, exon shuffling, and humanizing of monoclonal antibodies. Further, it presents strategies for improving the typical drawback associated with protein therapeutics including instability and limited penetration through biological barriers. This book covers various computational methods that are commonly used for designing therapeutic proteins and in silico method for predicting and improving in vivo efficacy of the therapeutic molecules. Lastly, the book highlights the recent advances in developing nanosized delivery systems to improve safety and efficacy of protein therapeutics. This book caters to students and researchers of medicinal chemistry, pharmaceutical sciences and therapeutics. It is also useful to clinicians working with therapeutic proteins.

This detailed volume provides state-of-the-art methodologies and reviews of important topics in the field of homology modeling. From homology modeling in the twilight zone and improving accuracy through sequence space analysis to approaches to construct multi-protein complex models, the book explores a wide variety of uses and applications of this valuable technique. Written for the highly successful Methods in Molecular Biology series, the chapters include introductions to their respective topics, lists of the necessary programs, webservers, and databases, step-by-step and readily reproducible protocols, as well as tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Homology Modeling: Methods and Protocols serves as an ideal guide to recent homology modeling procedures, assumptions made, and model quality assessment that will illuminate the black box of homology modeling for novice readers and broaden the knowledge of this methodology for professionals.

Redox Chemistry and Biology of Thiols offers an applied, comprehensive overview of redox chemistry and biology of thiol-dependent processes. Running from basic biology and chemistry of redox phenomena to research methods and highlighting recently identified roles of thiols across cellular and bodily systems, this book draws upon a range of disciplines to illuminate new research directions, new applications of thiol studies, and clinical translation. Sections cover thiol oxidizing species, thiol reactivity and modifications, thioredoxin, glutaredoxin, glutathione, peroxidases, thiol repair enzymes, thiol oxidative signaling, disulfide bond formation, thiol-based redox biosensors, cysteine and hydrogen sulfide metabolism, iron-sulfur cluster biogenesis, thiols in chloroplasts, blood thiols, sugar and polyamine thiols in pathogenic organisms, redox medicine (therapeutic applications of thiols and drug development), as well as methods and bioinformatics tools. - Runs from basic thiol biology and chemistry to applications and clinical translation - Provides methods and protocols that will power new research across biomedicine, cell biology, plant biology, drug development, and protein folding and modulation - Includes chapter contributions from international leaders in the field

This introduction collects 17 innovative approaches to engineer novel and improved proteins for diverse applications in biotechnology, chemistry, bioanalytics and medicine. As such, key developments covered in this reference and handbook include de novo enzyme design, cofactor design and metalloenzymes, extremophile proteins, and chemically resistant proteins for industrial processes. The editors integrate academic innovations and industrial applications so as to arrive at a balanced view of this multi-faceted topic. Throughout, the content is chosen to complement and extend the previously published two-volume handbook by the same editors, resulting in a superb overview of this burgeoning field.