Announcing a new publication for Acta Materia Medica journal. Proteins are essential macromolecules that perform functions according to their conformational dynamics. Studying the conformational changes induced by protein mutations is the standard approach used to understand the mechanisms underlying mutation-related physiological and pathological processes.
To enhance efficiency and decrease the expense of biological experiments, this paper introduces a method to generate mutated proteins through adversarial attacks on the AlphaFold2 (AF2) model. The structure change of adversarial protein sequences predicted by AF2 were explored compared to the wild type protein’s structure. CASP14 experiments indicated that altering only three residues via replacement, deletion, or insertion led to a 46.61 points difference in AF2’s predictions, according to the Local Distance Difference Test (lDDT).
The method was applied to the transmembrane lipid transporter SPNS2 to identify crucial residues and suggest potential alternative conformations, thereby streamlining the experimental phase in structure determination and mechanistic studies.
Source:
Journal reference:
Yuan, Z., et al. (2024). AF2-mutation: adversarial sequence mutations against AlphaFold2 in protein tertiary structure prediction. Acta Materia Medica. doi.org/10.15212/amm-2024-0047.
