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User's Manual for
EGAD! a Genetic Algorithm for protein Design!
(stand alone program)
  

EGAD's (Egad! a Genetic Algorithm for protein Design) main focus is performing protein design on fixed backbone scaffolds. All the major rotamer-optimization methods such as genetic algorithms (GA), monte carlo simulated annealing (MC), self-consistent mean-field optimization (SCMF), fast and accurate side-chain topology and energy refinement (FASTER), and dead-end elimination (DEE) have been implemented in EGAD. It can also consider multiple structures simultaneously for designing specific binding proteins or locking proteins into specific conformational states. In addition to natural protein residues, EGAD can also consider free-moving ligands with or without rotatable bonds. It may even be possible to use EGAD for drug design. EGAD can be used with a single processor, but it can take advantage of the power of parallelization to perform certain jobs quickly.

Some of the tasks EGAD can perform are:
    - prediction of mutation effects on protein stability and protein-complex formation to within ~1kcal/mol
    - automated scanning mutagenesis, including saturation mutagenesis, of proteins and protein complexes
    - total protein sequence design
    - design of ligand binding sites
    - optimization of sequences while considering multiple structures for the design of specific binding proteins, conformational switching, etc.
    - predicting the pK's of ionizable groups in proteins
    - generating tables to display the distribution of energetic interactions in protein structures
    - minimizing protein structure energies by adjusting dihedral angles

For a more complete discussion of protein design, please see my thesis and/or these other reviews (Pokala and Handel 2001; Kortemme and Baker 2004; Kuhlman and Baker 2004; Ventura and Serrano 2004; Pokala and Handel 2005).

This documentation is for the stand-alone EGAD program. Using this program does not require any programming knowledge.

Table of Contents (html)    or     download EGAD User's Manual (pdf)

Links:
    download the EGAD program with example files       installation instructions
    Table of Contents (html)    or     download EGAD User's Manual (pdf)
    examples/
    download Navin Pokala's Thesis (pdf)
    source_code/

If you use EGAD, please cite:
Pokala N, Handel TM. Energy functions for protein design: adjustment with protein-protein complex affinities, models for the unfolded state, and negative design of solubility & specificity. J Mol Biol. 347(1): 203-227. (2005). [download pdf]    [medline]

This program is distributed under the GNU public license (http://www.gnu.org/copyleft/gpl.html and COPYRIGHT_AND_LICENSE). It is provided as is, with absolutely no warranty expressed or implied.

The EGAD stand-alone program is no longer under active development. Nevertheless, I (Navin Pokala; navin @ annapurna . berkeley . edu) might be able to help you out, collaborate, and/or give you advice, depending on the problem. However, starting July 2005, I will be a postdoc studying C elegans neurobiology at The Rockefeller University in Cori Bargmann's lab, so the time I can dedicate may be limited.

Also check out the EGAD library project, which is under active development. This project is aimed primarily at programmers, although programs and scripts for end-users are available. You might also consider formally collaborating with the Handel lab.

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