ADL: Genotype and Phenotype

Stefano Forli forli at scripps.edu
Fri Nov 4 11:40:25 PDT 2011


Hi Malcolm,

On 11/04/2011 07:46 AM, Malcolm Stennett wrote:
>        I am running auto dock 4 and would like to ask you a few questions.
>
>   1. Could you explicitly describe what genotype and phenotype refer to in
> respect to the ligand and the protein. Is the genotype a set of mapping
> points and is the phenotype the bound ligand/protein complex?
Genotype and phenotype are terms of the genetic algorithm. The genotype is the 
'chromosome' containing all genes of a given ligand conformation (x,y,z position, 
orientation, torsions) in the population used during the search (ga_pop_size).
The phenotype is the representation of a given genotype, i.e. a given conformation of the 
ligand in a given position with respect to the protein.[1]
>
> 2. Could you explain how the genotype is able to move to the phenotype,
> then sample various local searches, and then finally form a new genotype
> from the more stable local search. In other words how does the lamarckian
> algorithm move forward and manage to form a new genotype? If i knew what
> genotype and phenotype refers to in the respect to the ligand and protein I
> would better be able to understand this.
When a conformation undergoes a local search step, only its phenotype is changed (i.e. the 
conformation is modified). If this leads to energy improvement, the genotype is changed to 
the values of the conformation at the end of the local search, otherwise the original 
genotype is left unchanged.[1]
>
> 3. What pH is the docking taking place? Did you choose to make all charged
> side chains neutral, all negatively charged, all positively charged, or is
> there a percentage of the later combinations? knowing the pH will help me
> figure this out.
The pH is defined by the protonation state of the inputs (ligand and receptor).
Basically, it depends on the hydrogens you add to your structures.
>
> 4. Is the desolvation referring to the the net free energy of water moving
> out of the binding site, or does this refer to the energy needed to remove
> water from the system, system meaning the whole ligand/protein complex.
Desolvation is calculated by AutoGrid only on the protein and stored in the desolvation 
map XXXXXXX.d.map. [2]
>
> Thank You for your help,
> Malcolm E. Stennett

For further details, please have a look at the AutoDock user guide [3] in the Appendix III 
for references.

Hope this helps,


Stefano


[1] Morris, G. M., Goodsell, D. S., Halliday, R.S., Huey, R., Hart, W.  E., Belew, R. K. 
and Olson,  A. J.  (1998), J. Computational Chemistry,  19:  1639-1662.  "Automated 
Docking  Using  a  Lamarckian Genetic Algorithm and and Empirical Binding Free Energy 
Function".

[2] Huey, R., Morris, G. M., Olson, A. J. and Goodsell, D. S.  (2007) J. Comput. Chem. 28, 
1145- 1152. "A semiempirical free energy force field with charge-based desolvation".

[3] 
http://autodock.scripps.edu/faqs-help/manual/autodock-4-2-user-guide/AutoDock4.2_UserGuide.pdf

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-- 
  Stefano Forli, PhD

  Research Associate
  Olson Molecular Graphics Laboratory
  Dept. Molecular Biology,  MB-112
  The Scripps Research Institute
  10550  North Torrey Pines Road
  La Jolla,  CA 92037-1000,  USA.

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     email: forli at scripps.edu
     http://www.scripps.edu/~forli/


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