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From Alignments to Structural Models
Summary Objectives Audience Format Outline Resources

   Course Summary

The National Center for Biotechnology Information (NCBI) presents From Alignments to Structural Models, a course including lectures and computer workshops where participants will first build and optimize structure-based multiple sequence alignments with Cn3D, and then use these alignments to generate 3D structural models in UCSF Chimera. This course is a continuation of the existing Exploring 3D Molecular Structures course.

   Scheduled Courses
Upcoming course at NLM - March 6, 2008
Courses in 2008 Previous Courses

   Course Materials
Lecture Slides Alignment Exercises
Course Handout Modeling Exercises
Chimera Quick Reference Modeling Guide

   Course Tools
Cn3D 4.2 UCSF Chimera
Chimera Script Generator SCWRL 3.0
Alignment Guide Amino Acid Explorer
PSSM Viewer  

   Course Objectives

After attending the course, participants should be able to do the following:

  • Create structure-based sequence alignments in Cn3D either from precalculated VAST/CDD alignments or from imported sequences and structures
  • Identify and correct problems in these alignments using Cn3D alignment editing tools
  • Use a Cn3D alignment as a guide to create a model 3D structure for a protein in UCSF Chimera by replacing residues, optimizing side chains rotamers and conducting simple energy minimizations
  • Export the new structure as a PDB file and import into Cn3D for direct comparisons with the original alignment

Summary Objectives Audience Format Outline Resources

   Intended Audience

The course is intended for principal investigators, postdoctoral fellows, graduate students, advanced undergraduates, and other scientific staff who are interested in creating structural models for proteins without solved structures. It is expected that participants will have either taken the Exploring 3D Molecular Structures course or will have an equivalent familiarity with Cn3D 4.1, Entrez Structure, VAST and Entrez Conserved Domains. While participants should also be familiar with basic computer operation and common Web browsers, no familiarity with UCSF Chimera, SCWRL 3.0 or other modeling software is assumed.

   Course Format

The course consists of two sessions, Creating Structure-based Alignments and Creating Structural Models. Each session requires 3.5 hr and includes a brief lecture followed by guided demonstrations and practical sessions during which participants will complete alignment editing and modeling projects.

Participants are welcome to bring their own projects or questions to the workshops.

Summary Objectives Audience Format Outline Resources

   Course Outline

Optimizing Structure-based Alignments

  • Alignment editing tools in Cn3D
  • Optimizing VAST alignments
  • Importing and aligning structures in Cn3D
  • Importing and aligning sets of sequences in Cn3D

Creating Structural Models

  • Overview of simple homology modeling
  • Introduction to UCSF Chimera
  • Preparing a template structure in Cn3D for Chimera
  • Creating, optimizing and minimizing a model structure
  • Importing the model structure into Cn3D

Summary Objectives Audience Format Outline Resources

   Course Resources

NCBI Databases:

NCBI Analysis Tools

  • Cn3D 4.2: This most recent version of Cn3D is currently available only for Windows operating systems as part of a bundle including CD-Tree 3.0; Mac and LINUX versions are coming soon, along with a Windows version independent of CD-Tree.
  • Cn3D 4.1: an increasingly powerful tool for viewing molecular structures and creating both structural and sequence alignments
  • Related Structures: a new service for creating sequence-structure alignments
  • CD-Search: Conserved Domain Search, or RPS-BLAST, for finding multiple alignments of conserved, functional domains that match a query protein
  • CDART: the Conserved Domain Architecture Retrieval Tool for finding proteins with similar domain architectures to a query protein
  • VAST: the Vector Alignment Search Tool for creating structural alignments
  • SALTO: the new Structure-based ALignment Tool for assembling structure-linked sequence alignments
  • NCBI Threader: software package for aligning a protein sequence to a 3D structure using associated multiple sequence alignments and chemical potentials, now available in Cn3D 4.1

UCSF Chimera

UCSF Chimera is an extensible package for viewing and analyzing molecular structures. It is freely available for a variety of platforms including Windows, Mac OS X and Linux, and is developed by the Resource for Biocomputing, Visualization, and Informatics at UCSF. Funding for the project comes from the National Center for Research Resources at NIH. Chimera has extensive online documentation.

SCWRL3.0

SCWRL3.0 is a command-line program for predicting the conformations of protein side chains. The software is freely available for researchers in non-profit institutions after obtaining a license (also free). SCWRL3.0 also runs on several platforms including Windows, Mac OS X and Linux. SCWRL3.0 was developed by Roland L. Dunbrack and co-workers at the Fox Chase Cancer Center.

   About the Instructors

Medha Bhagwat, Emir Khatipov, Rana Morris and Eric Sayers are biologists on the User Services staff of the National Center for Biotechnology Information.

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Revised January 2, 2008