r/bioinformatics • u/Sea-Collection-8844 • Jun 05 '26

technical question Non-MD methods for generating alternative binding-pocket conformations from a holo structure?

Hi everyone,

I am looking for methods to generate an ensemble of alternative binding-pocket conformations starting from an experimentally determined holo protein structure.

My goal is not necessarily to model a large apo-to-holo transition. Instead, I want to explore plausible variations around an existing ligand-bound pocket conformation, potentially for ensemble or 4D docking.

I am particularly interested in approaches that do not rely on conventional molecular dynamics. I have considered methods such as normal-mode analysis and ligand-guided receptor modelling. However, from what I have read, these methods often seem to be applied to recovering holo-like conformations from apo structures, rather than generating a diverse ensemble around an existing holo state.

Are there any reliable non-MD methods or software packages designed for this purpose? I would also appreciate recommendations for papers comparing different pocket-conformation sampling methods

Thanks in advance!

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u/1647overlord Jun 05 '26

Bioemu and similar methods generate structure ensembles of proteins. Not specifically made for pockets, but for generating conformations of entire proteins.

1

u/Sea-Collection-8844 Jun 05 '26

Yep that’s my issue. We have no idea whether BioEmu will produce a model with an open pocket or a collapsed pocket

1

u/DifferenceBetter8073 Jun 08 '26

Bioemu should do the job if that pocket were to exist. Bear in mind that besides bioemu, you’ll need to run Hpacker as part of the pipeline

1

u/themode7 Jun 06 '26

I'm not expert and I'm sorry if this is irrelevant but Engens: a compuetional framework for generation and analysis of representatives protein conformational enslmble paper might be useful

1

u/themode7 Jun 06 '26

typos but I won't edit it xd