Re: [GaMD-discuss] Peptide Gaussian Accelerated MD - Question about Simulation Set-up

[Arpan T. <agt...@nc...>]

 Shared files for GaMD equil.zip
<https://drive.google.com/file/d/1AfBLDE32c4p6P9cCrlur3-Ww4zrmnXlf/view?usp=drive_web>
Hello Prof. Yinglong,

Thank you for your reply! I have created a zip folder with all the
necessary files that are from the Pep-GaMD equilibration stage. I have also
attached a text file describing each file's contents. Some of the files
(md.out and trajectory file) are large in size and hence are being shared
via a drive link.

Thank you once again for helping us out!

Sincerely,
Arpan

On Fri, Jan 30, 2026 at 4:53 PM Miao, Yinglong <Yin...@me...>
wrote:

> Hi Arpan,
>
> Thanks for your interest in Pep-GaMD!
>
> Yes, it would be great if you can share your simulation input parameter
> files and probably mdout file for the Pep-GaMD equilibration. We can then
> look into the issue in more detail.
>
> Best regards,
> Yinglong
>
> Yinglong Miao, Ph.D.
> Associate Professor
> Department of Pharmacology
> Computational Medicine Program
> Lineberger Comprehensive Cancer Center
> University of North Carolina - Chapel Hill
> Tel: 1-919-962-5696
> http://miaolab.org
>
> Editor-in-Chief
> *npj Drug Discovery*
> https://www.nature.com/npjdrugdiscov
>
> On Jan 30, 2026, at 11:02 AM, Arpan Tapdiya <agt...@nc...> wrote:
>
> Hello Prof Miao,
>
> My name is Arpan Tapdiya, and I am a PhD student in Professor Carol Hall’s
> research group in the Department of Chemical and Biomolecular Engineering
> at North Carolina State University. Our group designs short peptides for
> biosensor and therapeutic applications. To do so, we have developed our
> Monte-Carlo based Peptide Binding Design Algorithm (PepBD), and we use
> molecular dynamics (MD) and enhanced sampling to quantify peptide-target
> interactions.
>
> I am currently applying Pep-GaMD to study binding dynamics for our
> designed 10-residue peptides interacting with a ~240-residue protein
> target. I set up simulations following the Pep-GaMD protocol from your
> paper <https://doi.org/10.1063/5.0021399> (with a larger solvent box for
> this system) and explored different boost settings, including varying σ0P
> and σ0D from ~2 to 6 kcal/mol.
>
> While the peptide behaves as expected by dissociating and exploring
> bound/unbound regions, during the GaMD equilibration stage (when the boost
> is applied to the target protein + solvent in the dual-boost scheme), the
> target protein begins to lose its native secondary structure. The target
> has four α-helices at the start of the simulation, but shortly after the
> Gaussian boost is applied, it progressively unfolds and appears
> intrinsically disordered. This occurs even at relatively small boost
> settings. Notably, the system remains stable in conventional MD without the
> GaMD boost.
>
> The target structure is taken from the Protein Data Bank, and the peptide
> was designed through our simulation workflow.
>
> I would be very grateful for your guidance on the following:
>
>    1.
>
>    What are the most common causes of target protein unfolding in
>    Pep-GaMD/GaMD runs?
>    2.
>
>    In your experience, can unfolding indicate that the boost potential is
>    effectively too aggressive for the system even when σ0P/σ0D are set low? If
>    so, what parameter adjustments or protocol changes would you recommend?
>    3.
>
>    Are there recommended strategies to maintain target stability in
>    Pep-GaMD without adding additional constraints, while still allowing
>    meaningful peptide binding/unbinding sampling?
>
> If helpful, I can share the simulation setup details and the necessary
> files.
>
> Thank you very much for your time and for developing and sharing
> GaMD/Pep-GaMD. This method is extremely valuable for the types of peptide
> systems we study, and we will be thankful for any help!
>
> Sincerely,
> Arpan
>
> --
> Arpan Tapdiya
> Graduate Student
> Department of Chemical and Biomolecular Engineering
> North Carolina State University
>
>
>

-- 
Arpan Tapdiya
Graduate Student
Department of Chemical and Biomolecular Engineering
North Carolina State University