| 1. |
- 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. |
- Rockey, William M., et al.
(författare)
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Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling
- 2011
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Ingår i: Nucleic Acid Therapeutics. - : Mary Ann Liebert. - 2159-3337 .- 2159-3345. ; 21:5, s. 299-314
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Tidskriftsartikel (refereegranskat)abstract
- RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several RNA aptamers that bind cancer cell-surface antigens with high affinity and specificity have been described. However, their clinical potential has yet to be realized. A significant obstacle to the clinical adoption of RNA aptamers is the high cost of manufacturing long RNA sequences through chemical synthesis. Therapeutic aptamers are often truncated postselection by using a trial-and-error process, which is time consuming and inefficient. Here, we used a rational truncation approach guided by RNA structural prediction and protein/RNA docking algorithms that enabled us to substantially truncateA9, an RNA aptamer to prostate-specific membrane antigen (PSMA),with great potential for targeted therapeutics. This truncated PSMA aptamer (A9L; 41mer) retains binding activity, functionality, and is amenable to large-scale chemical synthesis for future clinical applications. In addition, the modeled RNA tertiary structure and protein/RNA docking predictions revealed key nucleotides within the aptamer critical for binding to PSMA and inhibiting its enzymatic activity. Finally, this work highlights the utility of existing RNA structural prediction and protein docking techniques that may be generally applicable to developing RNA aptamers optimized for therapeutic use. © 2011 Mary Ann Liebert, Inc.
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| 4. |
- Shao, Linus Ruijin, 1964, et al.
(författare)
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Revealing the Hidden Mechanisms of Smoke-Induced Fallopian Tubal Implantation.
- 2012
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Ingår i: Biology of reproduction. - : Oxford University Press (OUP). - 1529-7268 .- 0006-3363. ; 86:4
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Tidskriftsartikel (refereegranskat)abstract
- Ectopic pregnancy (EP) is an enigmatic reproductive disorder. Although tubal EP is difficult to predict, several hypotheses about its etiology have been proposed. In retrospective case-control studies, smoking is associated with an increased rate of EPs in the Fallopian tube. Studies of experimental animals in vivo and human Fallopian tubal tissues in vitro have suggested mechanisms of Fallopian tubal damage and dysfunction induced by nicotine and other smoking-related chemicals that may explain this association. However, the pathogenesis of smoking-induced modulation of implantation leading to tubal EP is largely unknown. Since cigarette/tobacco smoke adversely affects the success of intrauterine implantation, there is a great need to determine how embryo implantation occurs in the Fallopian tube in female smokers of reproductive age.
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