Details

Autor(en) / Beteiligte

• Diwan, Gaurav D.
• Gonzalez-Sanchez, Juan Carlos
• Apic, Gordana
• Russell, Robert B.

Titel

Next Generation Protein Structure Predictions and Genetic Variant Interpretation

Ist Teil von

• Journal of molecular biology, 2021-10, Vol.433 (20), p.167180-167180, Article 167180

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] •Alphafold represents a major advance in computational biology in that it is now possible to predict protein topologies accurately from amino acid sequences.•The current abundance of known protein structures, however, suggests that the impact on much of biology, including genetic variant interpretation, could be less than anticipated.•There are certain protein classes, such as repeat, disordered or evolutionarily isolated proteins, for which additional effort is probably needed to predict accurately.•Larger proteins, protein complexes and functional insights are clearly the current challenges for the prediction community. The need to make sense of the thousands of genetic variants uncovered every day in terms of pathology or biological mechanism is acute. Many insights into how genetic changes impact protein function can be gleaned if three-dimensional structures of the associated proteins are available. The availability of a highly accurate method of predicting structures from amino acid sequences (e.g. Alphafold2) is thus potentially a great boost to those wanting to understand genetic changes. In this paper we discuss the current state of protein structures known for the human and other proteomes and how Alphafold2 might impact on variant interpretation efforts. For the human proteome in particular, the state of the available structural data suggests that the impact on variant interpretation might be less than anticipated. We also discuss additional efforts in structure prediction that could further aid the understanding of genetic variants.