The TMCrys server for supporting crystallization of transmembrane proteins

Varga, Julia K; Tusnády, Gábor

doi:10.1093/bioinformatics/btz108

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…We expanded this set with proteins that have high reliability (above>95%) topology prediction in the HTP. This dataset was then filtered for redundancy using CD-HIT [29], by decrementing identity (90, 70, 50 ,40) and word length (5,4,3,2). The list of collected proteins is available in Supplementary Table 1.…”

Section: Performance Of Alphafold On the Human Transmembrane Proteomementioning

confidence: 99%

“…The lipid bilayer surrounding the TMPs separates them into distinct phases, which require a multi-step folding process to properly encapsulate them 2 . Despite the crucial role that TMPs play in cellular processes, their structural characterization lags far behind that of globular proteins due to their natural dual environment 3 , which makes their purification and crystallization difficult 4 .…”

Section: Introductionmentioning

confidence: 99%

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How AlphaFold shaped the structural coverage of the human transmembrane proteome

Jambrich

Tusnády

Dobson

2023

Preprint

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AlphaFold2 (AF2) provides structures for every protein, opening up prospects for virtually every field in structural biology. However, transmembrane proteins pose a challenge for experimental scientists, resulting in a limited number of solved structures. Consequently, algorithms trained on this finite training set also face difficulties. To address this issue, we recently launched the TmAlphaFold database, where predicted AlphaFold2 structures are embedded into the membrane plane and a quality assessment is provided for each prediction using geometrical evaluation. In this paper, we analyze how AF2 has changed the structural coverage of membrane proteins compared to earlier years when only experimental structures were available, and high-throughput structure prediction was greatly limited. We also evaluate how AF2 can be used to search for (distant) homologs in highly diverse protein families. By combining quality assessment and homology search, we can pinpoint protein families where AF2 accuracy is limited, and experimental approaches are still desired.

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Section: Performance Of Alphafold On the Human Transmembrane Proteomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How AlphaFold shaped the structural coverage of the human transmembrane proteome

Jambrich

Tusnády

Dobson

2023

Preprint

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“…Several family members extrude xenobiotics (e.g., toxic molecules and therapeutic drugs) from the cell, thus, learning the substrate recognition mechanism of these multidrug transporters can improve drug development and may prevent unwanted drug interactions [ 2 , 7 ]. Consequently, determining the atomic level 3D structure of ABC proteins is a widely researched area [ 8 , 9 , 10 , 11 , 12 ]. For example, various steps of structure-based drug design, such as selecting the appropriate protein target, understanding its pathological mechanism at the molecular level, and developing a new therapeutic substance or redesigning a drug require the knowledge of the target protein structure at the atomic level [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology

Tordai

Suhajda

Sillitoe

et al. 2022

IJMS

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The number of unique transmembrane (TM) protein structures doubled in the last four years, which can be attributed to the revolution of cryo-electron microscopy. In addition, AlphaFold2 (AF2) also provided a large number of predicted structures with high quality. However, if a specific protein family is the subject of a study, collecting the structures of the family members is highly challenging in spite of existing general and protein domain-specific databases. Here, we demonstrate this and assess the applicability and usability of automatic collection and presentation of protein structures via the ABC protein superfamily. Our pipeline identifies and classifies transmembrane ABC protein structures using the PFAM search and also aims to determine their conformational states based on special geometric measures, conftors. Since the AlphaFold database contains structure predictions only for single polypeptide chains, we performed AF2-Multimer predictions for human ABC half transporters functioning as dimers. Our AF2 predictions warn of possibly ambiguous interpretation of some biochemical data regarding interaction partners and call for further experiments and experimental structure determination. We made our predicted ABC protein structures available through a web application, and we joined the 3D-Beacons Network to reach the broader scientific community through platforms such as PDBe-KB.

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How AlphaFold2 shaped the structural coverage of the human transmembrane proteome

Jambrich,

Tusnady,

Dobson

2023

Sci Rep

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AlphaFold2 (AF2) provides a 3D structure for every known or predicted protein, opening up new prospects for virtually every field in structural biology. However, working with transmembrane protein molecules pose a notorious challenge for scientists, resulting in a limited number of experimentally determined structures. Consequently, algorithms trained on this finite training set also face difficulties. To address this issue, we recently launched the TmAlphaFold database, where predicted AlphaFold2 structures are embedded into the membrane plane and a quality assessment (plausibility of the membrane-embedded structure) is provided for each prediction using geometrical evaluation. In this paper, we analyze how AF2 has improved the structural coverage of membrane proteins compared to earlier years when only experimental structures were available, and high-throughput structure prediction was greatly limited. We also evaluate how AF2 can be used to search for (distant) homologs in highly diverse protein families. By combining quality assessment and homology search, we can pinpoint protein families where AF2 accuracy is still limited, and experimental structure determination would be desirable.

show abstract

The TMCrys server for supporting crystallization of transmembrane proteins

Cited by 3 publications

References 13 publications

How AlphaFold shaped the structural coverage of the human transmembrane proteome

How AlphaFold shaped the structural coverage of the human transmembrane proteome

Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology

How AlphaFold2 shaped the structural coverage of the human transmembrane proteome

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