AlphaFold and the amyloid world.

By F. Pinheiro, Jaime Santos, S. Ventura. 2021

46 citations recorded by the source corpus.

Protein aggregation is a widespread phenomenon with important implications in many scientific areas. Although amyloid formation is typically considered as detrimental, functional amyloids that perform physiological roles have been identified in all kingdoms of life. Despite their functional and pathological relevance, the structural details of the majority of molecular species involved in the amyloidogenic process remains elusive. Here, we explore the application of AlphaFold, a highly accurate protein structure predictor, in the field of protein aggregation. While we envision a straightforward application of AlphaFold in assisting the design of globular proteins with improved solubility for biomedical and industrial purposes, the use of this algorithm for predicting the structure of aggregated species seems far from trivial. First, in amyloid diseases, the presence of multiple amyloid polymorphs and the heterogeneity of aggregation intermediates challenges the "one sequence, one structure" paradigm, inherent to sequence-based predictions. Second, aberrant aggregation is not the subject of positive selective pressure, precluding the use of evolutionary-based approaches, which are the core of the AlphaFold pipeline. Instead, amyloid polymorphism seems to be constrained by the need for a defined structure-activity relationship in functional amyloids. They may thus provide a starting point for the application of AlphaFold in the amyloid world.

Subfields: Materials Chemistry, Molecular Biology, Physiology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Materials Chemistry

1. Devlina Chakravarty
2. Yi Zhao
3. Zhenyu Yang
4. Runsheng Chen
5. Lauren L. Porter
6. Xiaoxi Zeng

In Molecular Biology

1. Devlina Chakravarty
2. Yi Zhao
3. Zhenyu Yang
4. Runsheng Chen
5. Lauren L. Porter
6. Xiaoxi Zeng

Citations in the corpus

• AlphaFold2 and its applications in the fields of biology and medicine (2023, background): “Furthermore, the initial conformation of EKP-GCSF from AF2 shows that the EKP which is around GCSF might provide evidence of the thermal-protectivity of EKP on GCSF. 176 Other applications .”
• AlphaFold2 fails to predict protein fold switching (2022, background): “30,31 TM-scores can sometimes mislead, especially when comparing mostly helical segments and/or highly dissimilar structures or sequences.”