Chapter 17 - How binding to surfaces affects disorder?

DI BARTOLO, ARY LAUTARO; MASONE, DIEGO

Structure and Intrinsic Disorder in Enzymology

Elsevier Academic Press

Lugar: Amsterdam; Año: 2023; p. 455 - 489

The biomedical and catalysis industries have been a driving force in the evolution of our understanding of protein functions. Detailed molecular information on the structure-to-function relation has been essential for developing new inhibitors and the rational design of new proteins. The availability of protein structures, mostly experimentally obtained by X-ray analysis, has been an enormous advantage since the first three-dimensional model of the myoglobin molecule in 1958. Recently in 2021, the artificial intelligence system AlphaFold was able to predict, for the first time, multiple 3D protein structures from their amino acid sequence with an accuracy that is starting to get comparable to experimental techniques. That, again, represents an enormous advantage to accelerate biomedical research. However, many proteins are unstructured under physiological conditions, and this characteristic is relatively common throughout the proteome. Moreover, protein intrinsic disorder has been suggested to be a crucial mechanism upon binding to membrane surfaces, with yet undescribed effects. Such problem remains difficult to approach with both experimental and computational techniques, making intrinsic disorder a new motivation for developing original methodologies that better describe its implications.