The molecular basis for cellular function of intrinsically disordered protein regions

AS Holehouse, BB Kragelund - Nature Reviews Molecular Cell Biology, 2024 - nature.com
Intrinsically disordered protein regions exist in a collection of dynamic interconverting
conformations that lack a stable 3D structure. These regions are structurally heterogeneous …

[HTML][HTML] Advances in protein structure prediction and design

B Kuhlman, P Bradley - Nature reviews molecular cell biology, 2019 - nature.com
The prediction of protein three-dimensional structure from amino acid sequence has been a
grand challenge problem in computational biophysics for decades, owing to its intrinsic …

[HTML][HTML] Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates

S Alberti, A Gladfelter, T Mittag - Cell, 2019 - cell.com
Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation
of membraneless compartments in cells. This realization has motivated major efforts to …

Mutation effects predicted from sequence co-variation

TA Hopf, JB Ingraham, FJ Poelwijk, CPI Schärfe… - Nature …, 2017 - nature.com
Many high-throughput experimental technologies have been developed to assess the
effects of large numbers of mutations (variation) on phenotypes. However, designing …

Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2

TR Alderson, I Pritišanac, Đ Kolarić… - Proceedings of the …, 2023 - National Acad Sciences
The AlphaFold Protein Structure Database contains predicted structures for millions of
proteins. For the majority of human proteins that contain intrinsically disordered regions …

Deep generative models of genetic variation capture the effects of mutations

AJ Riesselman, JB Ingraham, DS Marks - Nature methods, 2018 - nature.com
The functions of proteins and RNAs are defined by the collective interactions of many
residues, and yet most statistical models of biological sequences consider sites nearly …

A systematic p53 mutation library links differential functional impact to cancer mutation pattern and evolutionary conservation

E Kotler, O Shani, G Goldfeld, M Lotan-Pompan… - Molecular cell, 2018 - cell.com
The TP53 gene is frequently mutated in human cancer. Research has focused
predominantly on six major" hotspot" codons, which account for only∼ 30% of cancer …

Sixty-five years of the long march in protein secondary structure prediction: the final stretch?

Y Yang, J Gao, J Wang, R Heffernan… - Briefings in …, 2018 - academic.oup.com
Protein secondary structure prediction began in 1951 when Pauling and Corey predicted
helical and sheet conformations for protein polypeptide backbone even before the first …

The EVcouplings Python framework for coevolutionary sequence analysis

TA Hopf, AG Green, B Schubert, S Mersmann… - …, 2019 - academic.oup.com
Coevolutionary sequence analysis has become a commonly used technique for de novo
prediction of the structure and function of proteins, RNA, and protein complexes. We present …

Energy landscapes of protein aggregation and conformation switching in intrinsically disordered proteins

B Strodel - Journal of molecular biology, 2021 - Elsevier
The protein folding problem was apparently solved recently by the advent of a deep learning
method for protein structure prediction called AlphaFold. However, this program is not able …