# Peptide not flexible in docking

**URL:** <https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639>\
**Category:** HADDOCK\
**Created:** [October 31, 2023, 8:53am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639 "2023-10-31T08:53:56Z")\
**Posts on this page:** 6\
**Page:** 1

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**Author:** ![michael](https://avatars.discourse-cdn.com/v4/letter/m/4bbf92/32.png) [@michael](https://ask.bioexcel.eu/u/michael)\
**Post date:** [October 31, 2023, 8:53am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639/1 "2023-10-31T08:53:56Z")

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Hi,  
I built a peptide using pyPept but unfortunately, when I dock the peptides with my protein HADDOCK is unable to change the conformation of the peptide (the peptide in the docking results are too similar to the starting structure).  
I changed the following parameters in the run.cns file, are there any other parameters I should change?  
And just to ensure, did I define the fully flexible peptide correctly? it is segid B and set to malecule 2 (or should I have changed nfle\_2 also?  
I am using restraints of active and passive residues and local version.

Thank you!

{\* Fully flexible segments for molecule 2 _}  
{_ Note that current max is 5 (edit the run.cns to add more segments _}  
{===\>} nfle\_2=0;  
{_ Residues of molecule 2 at interface \*}  
{+ table: rows=5 “segment 1” “segment 2” “segment 3” “segment 4” “segment 5” cols=2 “Start residue” “End residue” +}  
{===\>} start\_fle\_2\_1=“5”;  
{===\>} end\_fle\_2\_1=“16”;

{\* number of MD steps for rigid body high temperature TAD _}  
{===\>} initiosteps=2000;  
{_ number of MD steps during first rigid body cooling stage _}  
{===\>} cool1\_steps=2000;  
{_ number of MD steps during second cooling stage with flexible side-chains at interface _}  
{===\>} cool2\_steps=4000;  
{_ number of MD steps during third cooling stage with fully flexible interface \*}  
{===\>} cool3\_steps=4000;

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<div class="post-metadata">

**Author:** ![amjjbonvin](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/amjjbonvin/32/23_2.png) [@amjjbonvin](https://ask.bioexcel.eu/u/amjjbonvin)\
**Post date:** [November 23, 2023, 9:19am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639/2 "2023-11-23T09:19:14Z")

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Your should set nfle\_2=1 is this case if you want your peptide to be fully flexible.

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<div class="post-metadata">

**Author:** ![michael](https://avatars.discourse-cdn.com/v4/letter/m/4bbf92/32.png) [@michael](https://ask.bioexcel.eu/u/michael)\
**Post date:** [November 23, 2023, 9:33am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639/3 "2023-11-23T09:33:44Z")

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Thank you!  
Does that mean then that it didn’t change the peptide to flexible from amino acids 5-16? since I didn’t do  
{===\>} nfle\_2=1;

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<div class="post-metadata">

**Author:** ![amjjbonvin](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/amjjbonvin/32/23_2.png) [@amjjbonvin](https://ask.bioexcel.eu/u/amjjbonvin)\
**Post date:** [November 23, 2023, 9:45am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639/4 "2023-11-23T09:45:33Z")

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Yes indeed

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<div class="post-metadata">

**Author:** ![michael](https://avatars.discourse-cdn.com/v4/letter/m/4bbf92/32.png) [@michael](https://ask.bioexcel.eu/u/michael)\
**Post date:** [November 23, 2023, 9:47am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639/5 "2023-11-23T09:47:57Z")

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OK  
But the docking results came out differently when I used flexible (in the wrong way) or didn’t use them. Is that because Haddock has some randomness involved? or it does still make some difference.

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<div class="post-metadata">

**Author:** ![amjjbonvin](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/amjjbonvin/32/23_2.png) [@amjjbonvin](https://ask.bioexcel.eu/u/amjjbonvin)\
**Post date:** [November 23, 2023, 10:04am UTC](https://ask.bioexcel.eu/t/peptide-not-flexible-in-docking/4639/6 "2023-11-23T10:04:27Z")

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There is indeed some chaotic nature to this type of computations, especially if run on different hardware. But I would not expect major differences unless some other parameter settings are changed.

And if you kept default settings for the semi-flexible segments your peptide would have some flexibility anyway