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Antibody Engineering, Methods and Protocols PDF

549 Pages·2004·5.588 MB·English
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MMeetthhooddss iinn MMoolleeccuullaarr BBiioollooggyy TTMM VOLUME 248 AAnnttiibbooddyy EEnnggiinneeeerriinngg MMeetthhooddss aanndd PPrroottooccoollss EEddiitteedd bbyy BBeennnnyy KK.. CC.. LLoo 1 Internet Resources for the Antibody Engineer Benny K.C.Lo and Yu Wai Chen 1.Introduction The Internet contains a wealth of information and tools that are relevant to various aspects of antibody engineering. Here, we present a collection of use- ful websites and software that is specific to antibody structure analysis and engineering,as well as for general protein analysis. Although this survey is by no means complete, it represents a good starting point. This list is accurate at the time of writing (August 2003). 2.List of Websites 2.1.Antibody-Specific Sites 2.1.1.The Kabat Database (G.Johnson and T.T.Wu, 2002; http://www.kabatdatabase.com) Created by E. A. Kabat and T. T. Wu in 1966, the Kabat database pub- lishes aligned sequences of antibodies,T-cell receptors,major histocompati- bility complex (MHC) class I and II molecules, and other proteins of immunological interest. A searchable interface is provided by the SeqhuntII tool, and a range of utilities is available for sequence alignment, sequence subgroup classification,and the generation of variability plots (seeChapter 2 for more details). 2.1.2.KabatMan (A.C.R.Martin, 2002; http://www.bioinf.org.uk/abs/simkab.html) This is a web interface to make simple queries to the Kabat sequence data- base. For more complex cases,queries should be sent directly in the KabatMan SQL-like query language. From:Methods in Molecular Biology, Vol.248:Antibody Engineering:Methods and Protocols Edited by:B.K.C.Lo ©Humana Press Inc., Totowa, NJ 3 4 Lo and Chen 2.1.3.IMGT, the International ImMunoGeneTics Information System® (M.-P.Lefranc, 2002;http://imgt.cines.fr) IMGT is an integrated information system that specializes in antibodies, T- cell receptors, and MHC molecules of all vertebrate species. It provides a com- mon portal to standardized data that include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, and two-dimensional (2D) and three-dimensional (3D) structures. IMGT includes three sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER- DB), one genome database (IMGT/GENE-DB), one 3D structure database (IMGT/3Dstructure-DB), and a range of web resources (“IMGT Marie-Paule page”) and interactive tools (seeChapter3 for more details). 2.1.4.V-BASE (I.M.Tomlinson, 2002; http://www.mrc-cpe.cam.ac.uk/vbase) V-BASE is a comprehensive directory of all human antibody germline vari- able region sequences compiled from more than one thousand published sequences. It includes a version of the alignment software DNAPLOT (devel- oped by Hans-Helmar Althaus and Werner Müller) that allows the assignment of rearranged antibody V genes to their closest germline gene segments. 2.1.5.Antibodies—Structure and Sequence (A.C.R.Martin, 2002;http://www.bioinf.org.uk/abs) This page summarizes useful information on antibody structure and sequence. It provides a query interface to the Kabat antibody sequence data, general information on antibodies, crystal structures, and links to other anti- body-related information. It also distributes an automated summary of all anti- body structures deposited in the Protein Databank (PDB). Of particular interest is a thorough description and comparison of the various numbering schemes for antibody variable regions. 2.1.6.AAAAA—AHo’s Amazing Atlas of Antibody Anatomy (A.Honegger, 2001;http://www.unizh.ch/~antibody) This resource includes tools for structural analysis,modeling,and engineer- ing. It adopts a unifying scheme for comprehensive structural alignment of antibody and T-cell-receptor sequences, and includes Excel macros for anti- body analysis and graphical representation. 2.1.7.WAM—Web Antibody Modeling (N.Whitelegg and A.R.Rees, 2001;http://antibody.bath.ac.uk) Hosted by the Centre for Protein Analysis and Design at the University of Bath,United Kingdom. Internet Resources 5 Based on the AbM package (formerly marketed by Oxford Molecular) to construct 3D models of antibody Fv sequences using a combination of estab- lished theoretical methods, this site also includes the latest antibody structural information. It is free for academic use (seeChapter 4 for more details). 2.1.8.Mike’s Immunoglobulin Structure/Function Page (M.R.Clark, 2001;http://www.path.cam.ac.uk/~mrc7/mikeimages.html) These pages provide educational materials on immunoglobulin structure and function, and are illustrated by many color images, models, and animations. Additional information is available on antibody humanization and Mike Clark’s Therapeutic Antibody Human Homology Project,which aims to corre- late clinical efficacy and anti-immunoglobulin responses with variable region sequences of therapeutic antibodies. 2.1.9.The Antibody Resource Page (The Antibody Resource Page, 2000;http://www.antibodyresource.com) This site describes itself as the “complete guide to antibody research and suppliers.”Links to amino acid sequencing tools,nucleotide antibody sequenc- ing tools, and hybridoma/cell-culture databases are provided. It also includes information on commercial suppliers,which is particularly useful for searching multiple suppliers for antibodies to your antigen of interest. 2.1.10.The Recombinant Antibody Pages (S.Dübel, 2000; http://www.mgen.uni-heidelberg.de/SD/SDscFvSite.html) This is a large collection of links and information on recombinant antibody technology and general immunology that provides links to companies that exploit antibody technology. 2.1.11.Humanization bY Design (J.Saldanha, 2000; http://people.cryst.bbk.ac.uk/~ubcg07s) This resource provides an overview on antibody humanization technology (seeChapter 7). The most useful feature is a searchable database (by sequence and text) of more than 40 published humanized antibodies including informa- tion on design issues,framework choice,framework back-mutations,and bind- ing affinity of the humanized constructs. 2.2.Primary Structure Analysis 2.2.1.ExPASy Molecular Biology Server (ExPASy, 2002; http://www.expasy.org) This all-in-one portal provides links to many other protein sequence and structure analysis sites, and includes the following sections: Databases, Tools 6 Lo and Chen and Software, Education, Documentation, and Links. Of these, the proteomic tools and databases are the most useful. 2.3.Three-Dimensional Structure Analysis and Graphics 2.3.1.O (A.Jones, 2002;http://xray.bmc.uu.se/~alwyn/o_related.html; note that the “official WWW server for O”:the O Files, http://www.imsb.au.dk/~mok/o, is now officially outdated). Love it or, hate it, O is still the indispensable graphics tool for structure rebuilding and analysis among protein crystallographers. However, the learn- ing curve is very steep. 2.3.2.Rasmol (Rasmol Home Page, 2000; http://www.umass.edu/microbio/rasmol/index2.htm) For ease of use,there is no replacement for Roger Sayle’s free program. This is a simple molecular graphics viewer that has an easy-to-use graphical inter- face. A newer version known as the Protein Explorer is gradually taking over (Eric Martz,2002; http://molvis.sdsc.edu/protexpl/frntdoor.htm). 2.3.3.PyMOL (DeLano Scientific, 2002;http://pymol.sourceforge.net) This is a relatively new development with the ambition to be the complete program to replace all other molecular graphics programs. It offers plenty of graphical features,such as an electron-density map and surface representations, includes an internal ray-tracer,and can produce publication-quality images. 2.3.4.WebLab ViewerLite (MSI, now Accelrys, 1999; http://molsim.vei.co.uk/weblab) Another molecular graphics program with a graphical user interface, this resource offers good rendering output. Development of this program has come to a halt. ViewerLite is free,but the extended-version ViewerPro is commercial. 2.3.5.DeepView (Swiss-Pdb Viewer) (N.Guex and T.Schwede, 2002; http://ca.expasy.org/spdbv) Swiss-PdbViewer is also a user-friendly graphics program that allows sev- eral proteins to be compared for structural alignments. It also offers many tools for structure analysis. Moreover, Swiss-PdbViewer is tightly linked to Swiss- Model,an automated homology modeling server (seeSubheading 2.5.1.). 2.3.6.GRASP (Graphical Representation and Analysis of Structural Properties) (A.Nicholls;http://trantor.bioc.columbia.edu/grasp) This is a highly original graphics program for the calculation and visualiza- tion of molecular properties. It is mostly used for analyzing electrostatic poten- Internet Resources 7 tials and surface complementarities. Although it has a graphical user interface, this program is not easy to use. Both academic and industrial users must buy a license. It is only available on the Silicon Graphics platform. 2.3.7.Uppsala Software Factory (G.J.Kleywegt, 2002; http://xray.bmc.uu.se/~gerard/manuals) Gerard Kleywegt’s huge collection of programs for structure analysis and structure data handling offers many utilities and macros that can enhance the power of the graphics program O (seeSubheading 2.3.1.). 2.4.Structural Analysis Databases 2.4.1.The Protein Data Bank (Research Collaboratory for Structural Bioinformatics, 2002;http://www.rcsb.org/pdb) This is the single worldwide repository for the processing and distribution of 3D biological macromolecular structure data. 2.4.2.SCOP (Structural Classification of Proteins) (The SCOP authors, 2002;http://scop.mrc-lmb.cam.ac.uk/scop) Originally developed by A. Murzin, S. Brenner, T. Hubbard, and C. Chothia,the SCOP database (hosted by the Medical Research Council Centre, Cambridge, UK) provides a detailed and comprehensive description of the structural and evolutionary relationships between all proteins with a known structure. 2.4.3.FSSP (Fold classification based on structure-structure alignment of proteins) (L.Holm, 1995;http://www.ebi.ac.uk/dali/fssp) Developed by L. Holm and C. Sander, the FSSP database is based on exhaustive all-against-all 3D structure comparison of protein structures in the Protein Data Bank. 2.5.Homology Modeling and Docking 2.5.1.Swiss-Model (T.Schwede , M.C.Peitsch and N.Guex, 2002; http://www.expasy.org/swissmod) This is a fully automated protein structure homology-modeling server, accessible via the ExPASy web server,or from the molecular graphics program DeepView (Swiss Pdb-Viewer; seeSubheading 2.3.5.). 2.5.2.Modeller (A.Sali group, 2002; http://www.salilab.org/modeller/modeller.html) Modeller is designed for homology or comparative modeling of protein 3D structures from a structure-based sequence alignment. This program,which has 8 Lo and Chen proven to be very popular among protein chemists, is a Unix-based program that is free for academic use. 2.5.3.CNS (Crystallography and NMR System) (Yale University, 2000; http://cns.csb.yale.edu) This is a very popular structure refinement package for structural scientists that includes many tools for structure analysis. For modeling purposes,it offers effective energy minimization protocols, including conventional energy mini- mization and simulated annealing. The commercial version,CNX,is marketed by Accelrys (http://www.accelrys.com/products/cnx). 2.5.4.CCP4 (Collaborative Computational Project, Number 4) Suite (CCP4, 2002;http://www.ccp4.ac.uk) Another very popular suite of programs among X-ray crystallographers,this suite consists of state-of-the-art utility programs covering all stages of protein crystallography. Among these, Refmac5 is a refinement program that offers structure idealization after homology model building. 2.5.5.XtalView (Scripps XtalView WWW Page, 2002; http://www.scripps.edu/pub/dem-web) XtalView is another highly regarded complete package for X-ray crystallog- raphy developed by D. McRee et al. at the Scripps Research Institute. It fea- tures a graphical user interface, and is relatively easy to use. It is very well-documented, and is accompanied by a textbook. Although it is free for academic use,commercial users must contact [email protected]. 2.5.6.Dock (Kuntz group, 1997; http://dock.compbio.ucsf.edu) This program, developed at the University of California, San Francisco, evaluates the chemical and geometric complementarity between a ligand and a receptor-binding site,and searches for favorable interacting orientations. 2.5.7.AutoDock (G.M.Morris, 2002;http://www.scripps.edu/pub/ olson-web/doc/autodock/) AutoDock is a suite of automated docking tools developed at the Scripps Research Institute,La Jolla,CA,that enables users to predict how small ligands bind to a receptor of known structure. 2.5.8.ICM-Dock (MolSoft, 2002;http://www.molsoft.com/products/ modules/dock.htm) ICM (Internal Coordinate Mechanics) uses an efficient and general global optimization method for structure design, simulation, and analysis. Within the Internet Resources 9 ICM-Main bundle,there is a module ICM-Dock that claims success in predict- ing protein-protein interactions and protein-ligand docking. Note: this is a commercial product. 2.6.Miscellaneous 2.6.1.Delphion (Delphion, Inc.;2002;http://www.delphion.com) This is an excellent gateway to information on granted U.S. and worldwide patents and patent applications. It requires mandatory registration and payment for selected services. 2 The Kabat Database and a Bioinformatics Example George Johnson and Tai Te Wu 1.Introduction In 1969, Elvin A. Kabat of Columbia University College of Physicians and Surgeons and Tai Te Wu of Cornell University Medical College began to col- lect and align amino acid sequences of human and mouse Bence Jones proteins and immunoglobulin (Ig) light chains. This was the beginning of the Kabat Database. They used a simple mathematical formula to calculate the various amino acid substitutions at each position and predict the precise locations of segments of the light-chain variable region that would form the antibody-com- bining site from a variability plot (1). The Kabat Databaseis one of the oldest biological sequence databases,and for many years was the only sequence data- base with alignment information. The Kabat Database was available in book form free to the scientific com- munity starting in 1976 (2), with an updated second edition released in 1979 (3), third edition in 1983 (4), fourth edition in 1987 (5), and fifth printed edi- tion in 1991 (6). Because of the inclusion of amino acid as well as nucleotide sequences of antibodies,T-cell receptors for antigens (TCR), major histocom- patibility complex (MHC) class I and II molecules, and other related proteins of immunological interest, it became impossible to provide printed versions after 1991. In that same year,George Johnson of Northwestern University cre- ated a website to electronically distribute the database located temporarily at: http://kabatdatabase.com During the following decade, the Kabat Database had grown more than five times. Thanks to the generous financial support from the National Institutes of Health,access to this website had been free for both academic and commercial use. With the completion of the human genome project as well as several other genome projects, scientific emphasis has gradually shifted from determining From:Methods in Molecular Biology, Vol.248:Antibody Engineering:Methods and Protocols Edited by:B.K.C.Lo ©Humana Press Inc., Totowa, NJ 11

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