Posts Predicting Protein 3D Structure

Predicting Protein 3D Structure

Basic Information

Christopher Burge, David Gifford, and Ernest Fraenkel. 7.91J Foundations of Computational and Systems Biology. Spring 2014. Massachusetts Institute of Technology: MIT OpenCourseWare, License: Creative Commons BY-NC-SA.

  • MIT 7.91J Foundations of Computational and Systems Biology🌎
  • Lecture 13




  • Align query to sequences in PDB
  • Use several alignment methods
  • Three categories of queries
    • High sequence similarity template(s) (>50% sequence similarity)
    • Medium sequence similarity template(s) (20-50% sequence similarity)
    • Low sequence similarity template(s) (<20% sequence similarity)
  • Refine models

General Refinement Procedure

  • Random changes to backbone torsion angles
  • Rotamer optimization of side chains
  • Energy minimization of torsion angles (bond lengths and angles kept fixed)
High sequence similarity template(s)
  • Minimal refinement, focus on regions where alignment is poor
  • Refine structures
  • Choose best model by final energy
Medium sequence similarity template(s)
  • Refinement focuses on regions near gaps and insertions, loops in the starting model, and sequence segments with low conservation
  • Replaces torsion angles with those from peptides of known structures
  • Minimize local structure
  • Refine global structure
Low sequence similarity template(s)
  • Use many more starting models
  • More aggressive refinement strategy
    • Rebuild secondary structure elements in addition to regions refined in medium homology
      • gaps and insertions
      • loops in the starting model
      • regions with low conservation

de novo


When there is no suitable homology model:

  • Monte Carlo search for backbond angles
    • Choose a short region (3-9 amino acids, Empirical) of backbone
    • Set torsion angles to those of a similar peptide in PDB
    • Accept with Metropolis Criteria
  • 36,000 MC steps
  • Repeat entire process to get 2,000 final structures
  • Cluster structures
  • Refine clusters
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