Empirical validation of ProteinMPNN's efficiency in enhancing protein fitness.

Abstract

Introduction: Protein engineering, which aims to improve the properties and functions of proteins, holds great research significance and application value. However, current models that predict the effects of amino acid substitutions often perform poorly when evaluated for precision. Recent research has shown that ProteinMPNN, a large-scale pre-training sequence design model based on protein structure, performs exceptionally well. It is capable of designing mutants with structures similar to the original protein. When applied to the field of protein engineering, the diverse designs for mutation positions generated by this model can be viewed as a more precise mutation range. Methods: We collected three biological experimental datasets and compared the design results of ProteinMPNN for wild-type proteins with the experimental datasets to verify the ability of ProteinMPNN in improving protein fitness. Results: The validation on biological experimental datasets shows that ProteinMPNN has the ability to design mutation types with higher fitness in single and multi-point mutations. We have verified the high accuracy of ProteinMPNN in protein engineering tasks from both positive and negative perspectives. Discussion: Our research indicates that using large-scale pre trained models to design protein mutants provides a new approach for protein engineering, providing strong support for guiding biological experiments and applications in biotechnology.