Hi
Im trying to build some stapled peptides for MD simulations on desmond. several papers have used schrodingers build module to build a helical peptide and then manually add the olefin staple but dont explain how they've assigned the bond angles, length partial charge etc needed for MD. Does anyone have any ideas how to assign these values?
thanks
Hi Mostafa,
first of all a small disclaimer: I have heard about, but never used Desmond, and I therefore the following answer will be rather general.
The values you want to assign are the basic parameters for your force-field that you are using.
The creation/assignment of these values is different for a lot of force-fields.
Some force-fields assign their data based on experimental data, and some use higher level QC calculations, such as DFT to generate the data.
The correct way of creating the data is therefore heavily dependent on the force-field you want to use. Most of them however describe in their initial publications how they have done it. My recommendation is to follow these original protocols if possible, some also list a way to do it in e.g. their FAQ. The data you generate must be in "balance" with the existing data.
If you can not find a protocol then here is something that can give you a starting guess, but requires a lot of checking (e.g. running MDs on the new residues for checking if known behavior is reproduced). You can run a DFT calculation (e.g. TPSS-D3BJ/def2-TZVP geometry optimization) on the new residue with a stump of what you want to connect to it, then generate multipole-derived charges (i'd say quadrupole one should do the trick). A frequency calculation can yield the parameters for bonds and angles (from the Hessian) this is however far from straight forward.
If you can afford it, then it is probably a good idea to run QM-MM calculations instead of just MM, here the QM part can be DFT of cause, but probably DTF-B or PM6-DH+ could also do the trick.
I hope this will help,
Jan
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