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- Lensink, Marc F., et al.
(författare)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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| 2. |
- Moretti, Rocco, et al.
(författare)
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Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
- 2013
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Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 81:11, s. 1980-1987
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Tidskriftsartikel (refereegranskat)abstract
- Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies. Proteins 2013; 81:1980-1987.
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| 3. |
- Vajda, Z., et al.
(författare)
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Transcranial Doppler-determined pulsatility index in the evaluation of endoscopic third ventriculostomy (preliminary data)
- 1999
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 141:3, s. 247-250
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Endoscopic 3rd ventriculostomy has become the method of choice in the management of occlusive hydrocephalus. The treatment is accompanied by significantly less peri-operative complications than the cerebrospinal fluid shunting procedures previously employed. Close surveillance of patients, however, is necessary to avoid the consequences of raised intracranial pressure that may develop in case of obstruction of the artificial outlet of the 3rd ventricle. The aim of this study was to confirm the value of transcranial Doppler-determined pulsatility index (PI) in the assessment of the patency of endoscopic 3rd ventriculostomy and to elucidate its usefulness in early postoperative recognition of increased intracranial pressure.Methods: In twenty-two patients suffering from occlusive hydrocephalus, transcranial Doppler sonography (TCD) was performed before, immediately after, and five days after endoscopic fenestration of the floor of the 3rd ventricle. PI was defined with fast Fourier transformation. Mean PI values were determined in both middle cerebral arteries (MCA), over five cardiac cycles.Results: In nineteen cases, PI values showed a significant decrease immediately as well as five days after the intervention as compared to the pre-operative values, and flow-sensitive MRI confirmed the patency of the fenestration in all cases. In one patient the operation failed to produce an effective diversion of cerebrospinal fluid as shown by flow-sensitive MRI, and the pulsatility index was unchanged. In two patients, a significant immediate postfenestration drop in PI was followed by a recurrence of PI to pre-operative levels without any clinical deterioration.Conclusions: Preliminary results suggest that the transcranial Doppler-determined pulsatility index is a useful non-invasive tool for the evaluation of the patency of the fenestration in the early follow-up of patients who underwent endoscopic third ventriculostomy.
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