Protein Modeling Workshop at UC Riverside (Nov. 8-9, 2002)

The goal of this workshop is to provide practical knowledge about protein modeling algorithms, tools and databases. Participants will be given hands‑on experience with sequence structure and domain databases, protein sequence and structure similarity searches, and protein modeling and docking. All software used in the Workshop is available as public Web servers or can be freely downloaded for academic use.

The lecture will follow a logical path from the basic notions used in description of protein sequence and structure, through the concept of sequence similarity, sequence‑structure relationship and similarities between protein structures, to protein‑protein interactions and drug design. Computer training will follow the parallel path from usage of the databases of protein sequences and structures, secondary structure prediction through sequence similarity searches to homology modeling and protein-protein docking. The workshop will be based in part on the “Principles of Protein Structure, Comparative Protein Modeling and Visualization” (http://www.expasy.org/swissmod/course/course-index.htm)

  1. Day: “Protein structure, domain databases, sequence and structure analysis”

-          Lecture:

o       Description of protein sequence and structure: protein sequence, secondary structure, backbone conformation, super-secondary structure, tertiary protein structure, folds, domains, quaternary structure.

o       Similarity between protein sequences ‑ concepts and algorithms.

o       Similarity between protein structures ‑ concepts and algorithms.

o       Relationship between protein sequence and structure – protein structure prediction.

-          Computer training:

o       Sequence databases (NCBI, Genebank, SwissProt)

§         Looking for sequences of interest

o       Sequence similarity searches with Blast and Psi-Blast

§         Predicting function of hypothetical proteins (Psi-blast)

§         Looking for new genes in the genomic data, verifying results

o       Sequence alignment and HMM databases (Pfam, Superfamily)

§         Predicting function of protein impossible to annotate with Psi‑blast

o       Threading methods (FFAS, Metaserver)

§         Predicting fold and function of the protein impossible to predict with Psi‑blast and HMM algorithms

o       Comparing alignments obtained with different methods (Blast, Psi‑blast, HMMs, FFAS)


 

o       Viewing protein 3D structures with Chime, SwissPdbView and Cn3D

§         Structure analysis (phosphorylation of tyrosine residue in dual-specificity phosphatases) (MMDB, CDD, Cn3D)

o       Protein structural databases (Pdb, Scop, Dali, Cath)

§         Looking for proteins of interest in structural databases

§         Comparing recently solved protein structure with known protein structures (Dali)

o       Secondary structure prediction (Jpred)

§         Verifying distant homology predictions

o       Structure similarity searches (CE, Dali)

§         Comparison of two structures with no detectable sequence similarity with (CE)

  1. Day: “Homology modeling and rational drug design”

-          Lecture:

o       “Significant sequence similarity usually implicates structure similarity” – the basis of homology modeling

o       Alignment accuracy and accuracy of models based on homology

o       Homology modeling algorithms

o       Side-chain rotamers and loop building

o       Possible applications of protein models of different accuracy

o       Problems of docking and rational drug design

-          Computer training:

o       Basic protein structure analysis with SwissPdbViewer:

§         Analysis of the active site

§         Building Loops

§         Building a functional unit from a monomer

o       Hands on work on specific modeling topics using the SwissPDBViewer (by Dimitrios Morikis)

o       Presentation of research examples on proteinprotein interactions (by Dimitrios Morikis)

o       Verification of modeling methods with test cases (proteins with known structures), checking structural similarity with (CE and SwissPdbViewer).

o       Protein‑protein docking (GRAMM).

 

WWW adresses of databases and tools used in the course:

 

Software, that can be downloaded and installed before the course: