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PMIpred: a physics-informed web server for quantitative protein-membrane interaction prediction.

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  • 1Leiden Institute of Chemistry, Leiden University, Leiden 2333 CC, Netherlands.

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Summary
This summary is machine-generated.

A new transformer neural network model accurately predicts membrane-binding free energy for peptides. This tool distinguishes curvature sensing from membrane binding and aids in discovering and designing membrane-interacting proteins.

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Area of Science:

  • Biophysics
  • Computational Biology
  • Protein Science

Background:

  • Peripheral membrane proteins transiently interact with lipid bilayers.
  • Predictive models for protein-membrane binding free energies are currently lacking.
  • Such tools are crucial for discovering and designing membrane-interacting motifs.

Purpose of the Study:

  • To develop a computational tool for predicting membrane-binding free energies of peptides.
  • To classify peptide membrane-associative activity (non-binding, curvature sensing, membrane binding).
  • To enable the detection of membrane-interaction regions in diverse proteins.

Main Methods:

  • Training a transformer neural network on over 50,000 peptide molecular dynamics simulations.
  • Developing a physics-informed model to predict relative membrane-binding free energy from amino acid sequences.
  • Benchmarking against state-of-the-art tools like DREAMM, PPM3, and MODA.

Main Results:

  • The model accurately predicts relative membrane-binding free energy for given amino acid sequences.
  • The model successfully classifies peptides into non-binding, curvature sensing, or membrane-binding categories.
  • The method demonstrates broad applicability across protein diversity and distinguishes curvature sensing from general membrane binding.

Conclusions:

  • The developed transformer model provides accurate predictions of peptide membrane-binding free energy.
  • The tool can differentiate between curvature sensing and general membrane binding.
  • The Protein-Membrane Interaction predictor (PMIpred) web server is available for public use.