Biology subjects

Freiberger, M. I.

Publications and source records attributed to Freiberger, M. I..

3 recordsLinked to original sources

bioRxiv2020

FrustratometeR: an R-package to compute Local frustration in protein structures, point mutants and MD simulations

Once folded, natural protein molecules have few energetic conflicts within their polypeptide chains. Many protein structures do however contain regions where energetic conflicts remain after folding, i. e. they have highly frustrated regions. These regions, kept in place over evolutionary and physiological timescales, are related to several functional aspects of natural proteins such as protein-protein interactions, small ligand recognition, catalytic sites and allostery. Here we present FrustratometeR, an R package that easily computes local energetic frustration on a personal computer or a cluster. This package facilitates large scale analysis of local frustration, point mutants and molecular dynamics (MD) trajectories, allowing straightforward integration of local frustration analysis into pipelines for protein structural analysis. Contactgonzalo.parra@embl.de Availability and implementationhttps://github.com/proteinphysiologylab/frustratometeR

bioinformatics↗

bioRxiv2020

Frustration in protein complexes leads to interaction versatility

Disordered proteins can fold into a well-defined structure upon binding but these complexes are often fuzzy: the originally disordered partner adopts different binding modes when bound to different partners. Here we perform a systematic analysis of 160 proteins that form fuzzy complexes and demonstrate that the disordered partner displays a high degree of frustration in both the free and bound states. Although the folding of disordered regions upon binding reduces frustration relative to that of the unbound state, the interactions at the binding interface do not become fully optimized. In addition, we show that sub-optimal interactions lead to alternative frustration patterns in the complexes with different partners. These results demonstrate that disordered proteins do not always achieve fully optimal interactions in their complexes and their residual frustration leads to interaction versatility with different partners.

bioinformatics↗

bioRxiv2019

Large Ankyrin repeat proteins are formed with similar and energetically favorable units

Ankyrin containing proteins are one of the most abundant repeat protein families present in all extant organisms. They are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Here, we build and curated a dataset of 200 thousand proteins that contain 1,2 million Ankyrin regions and characterize the abundance, structure and energetics of the repetitive regions in natural proteins. We found that there is a continuous roughly exponential variety of array lengths with an exceptional frequency at 24 repeats. We describe that individual repeats are seldom interrupted with long insertions and accept few deletions, consistently with the know tertiary structures. We found that longer arrays are made up of repeats that are more similar to each other than shorter arrays, and display more favourable folding energy, hinting at their evolutionary origin. The array distributions show that there is a physical upper limit to the size of an array of Ankyrin repeats of about 120 copies, consistent with the limit found in nature. Analysis of the identity patterns within the arrays suggest that they may have originated by sequential copies of more than one Ankyrin unit. Author summaryRepeat proteins are coded in tandem copies of similar amino acid stretches. We built and curated a large dataset of Ankyrin containing proteins, one of the most abundant families of repeat proteins, and characterized the structure of the arrays formed by the repetitions. We found that large arrays are constructed with repetitions that are more similar to each other than shorter arrays. Also, the largest the array, the more energetically favourable its folding energy is. We speculate about the mechanistic origin of large arrays and hint into their evolutionary dynamics.

bioinformatics↗