Announcing a brand new publication for the magazine. Proteins are essential macromolecules that perform functions in line with their conformational dynamics. Studying the conformational changes attributable to protein mutations is the usual approach to understanding the underlying mechanisms mutation-related physiological and pathological processes.
To extend the efficiency and reduce the price of biological experiments, this text presents a way to generate mutant proteins through adversarial attacks on the AlphaFold2 (AF2) model. The structural change of opposing protein sequences predicted by AF2 was examined as compared to the structure of the wild-type protein. CASP14 experiments showed that changing just three residues through alternative, deletion, or insertion resulted in a 46.61 point difference within the predictions of AF2 in line with the Local Distance Difference Test (lDDT).
The strategy was applied to the transmembrane lipid transporter SPNS2 to discover critical residues and suggest possible alternative conformations, streamlining the experimental phase in structure determination and mechanistic studies.
Source:
Magazine reference:
Yuan, Z., . (2024). AF2 mutation: adversarial sequence mutations against AlphaFold2 in predicting the tertiary structure of proteins. . doi.org/10.15212/amm-2024-0047.
