The Power of Bioinformatics by Vladimir N. Uversky

These flashcards cover essential vocabulary and concepts related to bioinformatics and the role of intrinsically disordered proteins in biological systems.

Bioinformatics

The use of databases and computers to ask and answer biological questions, involving computerized annotation (data bases)and manipulation of biological data(software tools).

Bioinformatics revealed that intrinsically disordered proteins carry out a wide variety of non-catalytic biological functions

Genomics

A field within bioinformatics that focuses on the sequencing and analysis of genomes.

Data Manipulation

The transformation and processing of biological data using software tools, an essential part of bioinformatics.

Functional Genomics

A subfield of genomics that aims to understand the function of genes and their interactions.

Intrinsic Disorder

Regions in proteins that do not have a stable or unique three-dimensional structure and can exist in multiple conformations(Highly abundant among signaling proteins)

Protein-Protein Interaction (PPI) Networks

Systems that describe how proteins interact within a cell, focusing on role of intrinsically disordered proteins.

Phosphorylation

Is a post-translational modification that adds a phosphate group to a protein in disordered regions .

Alternative Splicing

A process by which different combinations of exons are joined together to produce multiple protein isoforms from a single gene.

Post-Translational Modifications (PTMs)

Chemical modifications that occur on proteins after their synthesis which impacts their function and stability.

Flexibility of Intrinsic Disorder

The structural flexibility that allows intrinsically disordered proteins to interact with multiple partners and perform diverse functions.

Phosphorylation & native disorder

•>90% of eukaryotic proteins are phosphorylated;

•Each human protein kinase serves at least ~45 substrates;

•Each human phosphatase is expected to dephosphorylate ~100 clients;

•Few proteins ± phosphate in PDB;

•In PDB, nearly all eukaryotic protein sites without phosphate are natively disordered;

•Regions of native disorder commonly have phosphorylation sites;

Controlled Chaos/Concluding remarks

Disorder management inside the cell. As a result of fast mRNA degradation, slow translation of mRNA into protein, and fast protein degradation, the overall amount of intrinsically disordered proteins inside a cell is less, and their half-lives are generally shorter, than those of ordered proteins. However, some disordered proteins can be present at high quantities and for long periods of time if they are modified (such as by phosphorylation) or interact with some specific binding partners.

oIDPs are abundant in nature;

oIDPs possess unique structural properties;

oIDPs have recognizable sequence features and can be predicted;

oIDPs possess unique functional repertoire which complements functions of ordered proteins;

oDisorder is crucial for PPI;

oPTM sites are commonly located in disordered regions;

oIDPs are tightly controlled;

oIDPs are very common in human diseases;

oBioinformatics rules!

Intrinsically Disordered Proteins

In bioinformatics, IDP most commonly refers to Intrinsically Disordered Proteins. Unlike conventional proteins that fold into stable three-dimensional structures, IDPs exist as highly flexible, dynamic, and unstructured ensembles of conformations under physiological conditions. Their functional ability derives from this flexibility, a concept known as the "disorder-function paradigm," which complements the traditional "structure-function paradigm"