| 1. |
- Cheng, Jianlin, et al.
(författare)
-
Estimation of model accuracy in CASP13
- 2019
-
Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 87:12, s. 1361-1377
-
Tidskriftsartikel (refereegranskat)abstract
- Methods to reliably estimate the accuracy of 3D models of proteins are both a fundamental part of most protein folding pipelines and important for reliable identification of the best models when multiple pipelines are used. Here, we describe the progress made from CASP12 to CASP13 in the field of estimation of model accuracy (EMA) as seen from the progress of the most successful methods in CASP13. We show small but clear progress, that is, several methods perform better than the best methods from CASP12 when tested on CASP13 EMA targets. Some progress is driven by applying deep learning and residue‐residue contacts to model accuracy prediction. We show that the best EMA methods select better models than the best servers in CASP13, but that there exists a great potential to improve this further. Also, according to the evaluation criteria based on local similarities, such as lDDT and CAD, it is now clear that single model accuracy methods perform relatively better than consensus‐based methods.
|
|
| 2. |
- Durairaj, Janani, et al.
(författare)
-
Uncovering new families and folds in the natural protein universe
- 2023
-
Ingår i: Nature. - 0028-0836. ; 622:7983, s. 646-653
-
Tidskriftsartikel (refereegranskat)abstract
- We are now entering a new era in protein sequence and structure annotation, with hundreds of millions of predicted protein structures made available through the AlphaFold database1. These models cover nearly all proteins that are known, including those challenging to annotate for function or putative biological role using standard homology-based approaches. In this study, we examine the extent to which the AlphaFold database has structurally illuminated this "dark matter" of the natural protein universe at high predicted accuracy. We further describe the protein diversity that these models cover as an annotated interactive sequence similarity network, accessible at https://uniprot3d.org/atlas/AFDB90v4 . By searching for novelties from sequence, structure, and semantic perspectives, we uncovered the β-flower fold, added multiple protein families to Pfam database2, and experimentally demonstrate that one of these belongs to a new superfamily of translation-targeting toxin-antitoxin systems, TumE-TumA. This work underscores the value of large-scale efforts in identifying, annotating, and prioritising novel protein families. By leveraging the recent deep learning revolution in protein bioinformatics, we can now shed light into uncharted areas of the protein universe at an unprecedented scale, paving the way to innovations in life sciences and biotechnology.
|
|
| 3. |
- Thorin, Eva, 1967-, et al.
(författare)
-
DRY DIGESTION PILOT TESTS USING RESIDUAL MUNICIPAL WASTE AS SUBSTRATE
- 2015
-
Ingår i: Sardinia 2015. - Padova : CISA publisher. - 9788862650212
-
Konferensbidrag (refereegranskat)abstract
- A pilot plug-flow dry digestion process was tested for production of biogas from the fine fraction of the residual municipal solid waste after source sorting of the organic fraction of the waste. The residual waste is complex, containing a mix of hard and soft plastic, paper, metal, glass, and a varying amount of organic material. The utilization as a substrate for biogas production is therefore challenging. The purpose of the pilot tests was to determine if it is technically feasible to produce biogas from this waste. The plant was operated under thermophilic conditions for almost three months. In parallel also a garage fermentation batch pilot plant was tested with the same substrate. The results from the tests are promising concerning the biogas production even if there are indications that the process in the plug-flow reactor was operated in so called inhibited steady state at the higher loading rates.
|
|
| 4. |
- Vighi, Eleonora, et al.
(författare)
-
Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration
- 2018
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:13, s. 2997-3006
-
Tidskriftsartikel (refereegranskat)abstract
- Inherited retinal degeneration (RD) is a devastating and currently untreatable neurodegenerative condition that leads to loss of photoreceptor cells and blindness. The vast genetic heterogeneity of RD, the lack of “druggable” targets, and the access-limiting blood–retinal barrier (BRB) present major hurdles toward effective therapy development. Here, we address these challenges (i) by targeting cGMP (cyclic guanosine- 3′,5′-monophosphate) signaling, a disease driver common to different types of RD, and (ii) by combining inhibitory cGMP analogs with a nanosized liposomal drug delivery system designed to facilitate transport across the BRB. Based on a screen of several cGMP analogs we identified an inhibitory cGMP analog that interferes with activation of photoreceptor cell death pathways. Moreover, we found liposomal encapsulation of the analog to achieve efficient drug targeting to the neuroretina. This pharmacological treatment markedly preserved in vivo retinal function and counteracted photoreceptor degeneration in three different in vivo RD models. Taken together, we show that a defined class of compounds for RD treatment in combination with an innovative drug delivery method may enable a single type of treatment to address genetically divergent RD-type diseases.
|
|
