Homology Modeling: Concepts and Protocols S. Ravichandran, Ph.D.

Class Location: ABCC I-Floor (Bldg 430), NCI-Frederick, MD
Date: June 14 (Wednesday), 2006; Time: 9:30 AM - 12:30 PM 

Goal: Basic concepts of homology modeling will be intoduced at an elementary level. Tripos Sybyl (& Insight, Homology) software will be used for visualization and homology modeling. Some of the closely related topics like sequence similarity, structural similarity, database searching, loop modeling, identifying correct/incorrect models will also be discussd. A homology modeling hands-on exercise will be carried out starting from a protein sequence using the homology module in InsightII (Accelrys).

Click here to go back to my class web-page.

Exercise[1a]: Getting familiarize with Swiss-PdbViewer. Click here to open 
the hands-on notes 
Exercise[1b]: Exploring the active site of Pseudomonas 7A Glutaminase-
Asparaginase. Click here to open the hands-on notes.

Exercise2: Homology modeling with Swiss-PdbViewer. Click here to open 
the hands-on instruction page.

1. CASP Protein Structure Prediction Center, Genome Center, Univ California, Davis
2. Swiss-Model Server (Free)
3. CPH Models Server
4. Wloop The Loop Homology Modeling Server
5. What-If Server V.Friend's What-IF Homology Modeling Server
6. Composer Tripos Sybyl's Homology Modeling tools. Also includes Matchmaker and GeneFold software.
7. UCLA/DOE Server UCLA/DOE Fold Server
8. Predict Protein Server EMBL, Predict Protein Server
9. Abagyan Lab Server Scripps Research Institute
10. 3D-Jigsaw Comparative Modelling Server UK Site. Click on submission to submit the sequence.

1. Swiss-Model Repository
2. ModBaseDatabase of 3D models solved using Comparative Modeling (Modeller)

1. 3D-PSSM UK Site. A Fast, web-based method for protein fold recognition using 1D and 3D sequences.
2. DALI Server Server for comparing protein structures in 3D
3. SAM-T02 HMM-based protein structure prediction
4. FUGUE FUGUE Profile Library Search Against Homstrad [University of Cambridge, Dept. of Biochemistry, Prof. Blundell's group)
   1. HOMSTRAD Homologous Structure Alignment Database

1. Predict Protein Server The Predict Protein Server
2. JPRED Server Barton Group Secondary Structure Prediction Server
3. PSIPERD Secondary Structure Prediction Server
4. EVA EVA continously and automatically analyses protein structure prediction servers in 'real time'
5. SAM-T02 HMM-based Protein Structure Prediction

1. Protscale Expasy web-site for hydrophobicity prediction
2. TMHMM Predicting transmembrane regions using Hidden Markov Models. This site is maintained by Center for Biological Aanalysis (CBS), the Technical University of Denmark.
3. PHDhtm PHDhtm TRANSMEMBRANE HELICES PREDICTION

1. SPDBV Swiss-PDB Viewer
2. Cn3D See in 3-D
3. Protein Explorer (Previous version, Rasmol)
   • Rasmol Rasmol Animations
4. DSVisualizer Windows, Linux Platform
5. VMD Windows, Linux and other platforms

1. Sybyl Tripos (Composer, Match-maker etc.)
2. InsightII Accelrys (GCG, InsightII, Homology, Modeler, DS Modeling etc.)
3. Modeller (Free for Academics & Non-profit institutions)
4. GeneMine Formerly known as Xlook
5. MOE Molecular Operating Environment (MOE)
6. PRIME Protein Structure Prediction
7. Swiss-Model Swiss-Model:Protein Structure Prediction
8. Pro-Fit ProFit: Least Squares Fitting software

1. Medline NCBI-Medline

1. GenBank NCBI-Gene Bank
   1. INSDC International Nucleotide Sequence Database Collaboration
2. GenScan. Gene Scanning and identification.
3. Translate Expassy Translation tools
4. EMBL European Molecular Biology
5. European Bioinformatics Institute (EBI)
6. BSM Biomolecular and Structure Modelling Group, UCL, UK
7. UniProt ExPassy: Access to databases Swiss-Prot, TrEMBL, Prosite, SWISS-2DPAGE, ENZYME, SWISS-MODEL Repository, CD40Lbase, SeqAnalRef from ExPASy home page
8. PIR Protein Information Resource
9. nrl3d NRL-3D
10. RESID RESID database is a comprehensive collection of annotations and structures for post-translational modifications.

1. NR All non-redundant GenBank CDS translations+RefSeq Proteins +PDB+SwissProt+PIR+PRF
2. OWL non-redundant datbase of four publically available sources Swiss-Prot, PIR(1-3), GenBank (translation) and NRL-3D.
3. Swiss-Prot+TrEMBL Swiss-Prot Composite Database

1. Prosite Database of protein families and domains.
2. PRINTS Protein FingerPrint Database. Search initiated from BLOCKS database uses PRINTS fingerprint database
3. BLOCKS Uses INTERPRO database from EMBL
4. PFAM Protein families database of alignments and Hidden Markov Models
5. ClustalW Multiple Sequence Alignment software from EMBL-EBI

1. PDB Protein Data Bank
2. MMDB Molecular Modeling DataBase: A database of 3D structures, as well as tools for their visualization and analysis.
3. SCOP Structural Classification of Proteins
4. PDBsum (Prof. Thornton Group software) A database of known 3D strucutres of proteins and nucleic acids
5. CATH Protein Structure Classification
6. FSSP Fold classification based on Structure-Structure alignment of Proteins

1. FATCAT: Flexible structure AlignmenT by Chaining Aligned fragment pairs following Twists, Burham Institute for Medical Research, La Jolla, CA
2. FAST Fast Alignment and Search Tool: Boston University Bioinformatics
3. SuperPose Protein Superposition server, University of Alberta, Canada
4. K2SA Protein Superposition server, Boston University
5. CE Protein Structure Comparision and Alignment using Combinatorial Extension (CE) Method
6. Protein3Dfit Cologne University Bioinformatics, Cologne, Germany
7. MAMMOTH MAtching Molecular Models Obtained from THeory, Mount Sinai School of Medicine, NY
8. MatchMaker (Chimera) carries out sequence alignment and use the information to carry out Structural Alignments.

• 3DCOFEE CNRS, France

DBAli, HOMSTRAD, S4

• UCSF

1. Procheck Stereo-chemical quality of protein and residue by residue analysis in figures
2. PDBreport Report of PDB files

1. Delphi Commercial Version of Delphi. A module in InsightII.
2. Grasp A Molecular Visualization and analysis program. It is particularly useful for the display and manipulation of the surfaces of molecules and their electrostatic properties.

1. Biochemical Pathways Expassy
2. aMAZE EMBL: Protein Function and Biochemical Networks
3. KEGG Kyoto Encyclopedia of Genes and Genomes

1. Sequence comparison and protein structure prediction, Roland L Dunbrack Jr. Cur. Opin. Str. Biol, 2006, 16:374
2. A Comparative Study of Available Software for high-accuracy homology modeling: From sequence alignments to structural models, Akbar Nayeem et al, Protein Science, 2006 15:808 Servers for protein structure prediction, D. Fischer, Curr Opin. Str. Biology, 2006, 16:179
3. In Quest of an empirical potential for protein structure prediction, J. Skolnick, Curr. Opin Str. Biology, 2006, 16:166
4. Comparative modeling for protein structure prediction, Krzysztof Ginalski, Cur. Opin Str. Biology, 2006, 16:172-177
5. Sequence Similarity, talk by Prof. W.R. Pearson, 2006
6. Predicting protein function from sequence and structural data, J.D. Watson, R.A. Laskowski and J.M. Thornton, Cur. Opin Strl. Biology, 2005, 15:275-284
7. Application and Limitations of X-ray crystallographic Data in Structure-based Ligand and Drug Design, Andrew M. Davis, Simon J Teague and Gerard J. Kleywegt, Angew. Chem. Int. Ed 2003, 42, 2718-2736
8. From protein structure to biochemical function? R.A. Laskowski, J.D. Watson and J.M. Thornton, J Str and Funct. Genomics, 2003 4:167
9. Sequence and Structure differences between enzyme and nonenzyme homologs, A.E. Todd, C.A. Orango and J.M. Thornton, Structure, 2002, 10:1435-1451
10. Validation of protein crystal structures, G. J. Kleywegt, Acta Crystallographica Sec D, 2000, D56, 249

web-links:
• Molecular Modeling for Beginners Tutorial for Deep View (Swiss-PdbViwer)
• Principles of Protein Structure Principles of Protein Structure, Comparative Protein Modelling and Visualisation by Nicolas Guex and Manuel C. Peitsch
• Homology Modeling Course CMBI Homology Modelling Course
• Homology Modeling
• Homology Modeling Using Midas
• Comparative Modeling For Beginners
Books:
• Crystallography Made Crystal Clear: A guide for users of macromolecular models, Gale Rhodes, 3rd Edition (2006)
• Bioinformatics: Sequence and Genome Analysis, Second Edition David W. Mount (2004)
• BLAST: An essential Guide to the Basic Local Alignment Search Tool, Ian Korf, Mark Yandell and Joseph Bedell, O'Reilly, 2003.
• Structural Bioinformatics, Edited by Philip E. Bourne, Helge Weissig (2003).
• Sequence Analysis in a Nutshell: A Guide to Tools and Databases Scott Markel, Kristine Conner, Darryl Leon (2003)
• Introduction to Protein Structure" by Branden & Tooze, Second Edition (1999)

Contact Info: Dr. S. Ravichandran
              Advanced Biomedical Computing Center,
              NCI-Frederick, NIH
              Bldg 430, Frederick, MD 21702
              Tel:  301-846-1991
              Email: sravi at ncifcrf dot gov
              Web: 
              http://ncisgi.ncifcrf.gov/~ravichas