MemConverter: An Iterative Pipeline for Reprogramming Protein Localization in Membrane or Aqueous Solution

We propose a pipeline, MemConverter, for the conversion of soluble proteins to membrane proteins and vice versa, based on the prediction of membrane contact probability (MCP). By fine-tuning ProteinMPNN with a membrane protein dataset to create MemProtMPNN, and integrating it with iterative structure refinement using AlphaFold2, our approach enables precise reprogramming of protein surface properties. The pipeline utilizes MCP-guided sequence fusion to direct the evolution of protein sequences towards the desired membrane or soluble environments. During this process, selective residues are fixed to concentrate design efforts on regions requiring alteration. The pipeline demonstrates superior performance compared to existing methods, and molecular dynamics simulations validate that the designed proteins exhibit stable membrane integration or enhanced solubility, depending on the target localization. This pipeline introduces a novel computational tool for engineering proteins to be localized in membranes or aqueous solutions.