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1. Guiding Protein Conformation Sampling with Conformation Space Maps

   https://doi.org/10.29007/gfdc  

   Zaman, Ahmed Bin; De Jong, Kenneth; Shehu, Amarda (March 2022, EPiC Series in Computing)

   Deep learning research, from ResNet to AlphaFold2, convincingly shows that deep learning can predict the native conformation of a given protein sequence with high accu- racy. Accounting for the plasticity of protein molecules remains challenging, and powerful algorithms are needed to sample the conformation space of a given amino-acid sequence. In the complex and high-dimensional energy surface that accompanies this space, it is critical to explore a broad range of areas. In this paper, we present a novel evolutionary algorithm that guides its optimization process with a memory of the explored conformation space, so that it can avoid searching already explored regions and search in the unexplored regions. The algorithm periodically consults an evolving map that stores already sampled non- redundant conformations to enhance exploration during selection. Evaluation on diverse datasets shows superior performance of the algorithm over the state-of-the-art algorithms. 

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2. Indian Ocean Dipole leads to Atlantic Niño

   https://doi.org/10.1038/s41467-021-26223-w  

   Zhang, Lei; Han, Weiqing (October 2021, Nature Communications)

   Abstract Atlantic Niño is the Atlantic equivalent of El Niño-Southern Oscillation (ENSO), and it has prominent impacts on regional and global climate. Existing studies suggest that the Atlantic Niño may arise from local atmosphere-ocean interaction and is sometimes triggered by the Atlantic Meridional Mode (AMM), with overall weak ENSO contribution. By analyzing observational datasets and performing numerical model experiments, here we show that the Atlantic Niño can be induced by the Indian Ocean Dipole (IOD). We find that the enhanced rainfall in the western tropical Indian Ocean during positive IOD weakens the easterly trade winds over the tropical Atlantic, causing warm anomalies in the central and eastern equatorial Atlantic basin and therefore triggering the Atlantic Niño. Our finding suggests that the cross-basin impact from the tropical Indian Ocean plays a more important role in affecting interannual climate variability than previously thought. 

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3. Adaptive Stochastic Optimization to Improve Protein Conformation Sampling

   https://doi.org/10.1109/TCBB.2021.3134103  

   Zaman, Ahmed Bin; Inan, Toki Tahmid; De Jong, Kenneth; Shehu, Amarda (January 2021, IEEE/ACM Transactions on Computational Biology and Bioinformatics)

   We have long known that characterizing protein structures structure is key to understanding protein function. Computational approaches have largely addressed a narrow formulation of the problem, seeking to compute one native structure from an amino-acid sequence. Now AlphaFold2 promises to reveal a high-quality native structure for possibly many proteins. However, researchers over the years have argued for broadening our view to account for the multiplicity of native structures. We now know that many protein molecules switch between different structures to regulate interactions with molecular partners in the cell. Elucidating such structures de novo is exceptionally difficult, as it requires exploration of possibly a very large structure space in search of competing, near-optimal structures. Here we report on a novel stochastic optimization method capable of revealing very different structures for a given protein from knowledge of its amino-acid sequence. The method leverages evolutionary search techniques and adapts its exploration of the search space to balance between exploration and exploitation in the presence of a computational budget. In addition to demonstrating the utility of this method for identifying multiple native structures, we additionally provide a benchmark dataset for researchers to continue work on this problem. 

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4. Algal-fungal symbiosis leads to photosynthetic mycelium

   https://doi.org/10.7554/eLife.47815  

   Du, Zhi-Yan; Zienkiewicz, Krzysztof; Vande Pol, Natalie; Ostrom, Nathaniel E; Benning, Christoph; Bonito, Gregory M (July 2019, eLife)

   Yeast, molds and other fungi are found in most environments across the world. Many of the fungi that live on land today form relationships called symbioses with other microbes. Some of these relationships, like those formed with green algae, are beneficial and involve the exchange carbon, nitrogen and other important nutrients. Algae first evolved in the sea and it has been suggested that symbioses with fungi may have helped some algae to leave the water and to colonize the land more than 500 million years ago. A fungus called Mortierella elongata grows as a network of filaments in soils and produces large quantities of oils that have various industrial uses. While the details of Mortierella’s life in the wild are still not certain, the fungus is thought to survive by gaining nutrients from decaying matter and it is not known to form any symbioses with algae. In 2018, however, a team of researchers reported that, when M. elongata was grown in the laboratory with a marine alga known as Nannochloropsis oceanica, the two organisms appeared to form a symbiosis. Both the alga and fungus produce oil, and when grown together the two organisms produced more oil than when the fungus or algal cells were grown alone. However, it was not clear whether the fungus and alga actually benefit from the symbiosis, for example by exchanging nutrients and helping each other to resist stress. Du et al. – including many of the researchers involved in the earlier work – have now used biochemical techniques to study this relationship in more detail. The experiments found that there was a net flow of carbon from algal cells to the fungus, and a net flow of nitrogen in the opposite direction. When nutrients were scarce, algae and fungi grown in the same containers grew better than algae and fungi grown separately. Further, Mortierella only obtained carbon from living algae that attached to the fungal filaments and not from dead algae. Unexpectedly, further experiments found that when grown together over a period of several weeks or more some of the algal cells entered and lived within the filaments of the fungus. Previously, no algae had ever been seen to inhabit the living filaments of a fungus. These findings may help researchers to develop improved methods to produce oil from M. elongata and N. oceanica. Furthermore, this partnership provides a convenient new system to study how one organism can live within another and to understand how symbioses between algae and fungi may have first evolved. 

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5. Proteasomal conformation controls unfolding ability

   https://doi.org/10.1073/pnas.2101004118  

   Cresti, Julianna R.; Manfredonia, Abramo J.; Bragança, Christopher E.; Boscia, IV, Joseph A.; Hurley, Christina M.; Cundiff, Mary D.; Kraut, Daniel A. (June 2021, Proceedings of the National Academy of Sciences)

   The 26S proteasome is the macromolecular machine responsible for the bulk of protein degradation in eukaryotic cells. As it degrades a ubiquitinated protein, the proteasome transitions from a substrate-accepting conformation (s1) to a set of substrate-processing conformations (s3 like), each stabilized by different intramolecular contacts. Tools to study these conformational changes remain limited, and although several interactions have been proposed to be important for stabilizing the proteasome’s various conformations, it has been difficult to test these directly under equilibrium conditions. Here, we describe a conformationally sensitive Förster resonance energy transfer assay, in which fluorescent proteins are fused to Sem1 and Rpn6, which are nearer each other in substrate-processing conformations than in the substrate-accepting conformation. Using this assay, we find that two sets of interactions, one involving Rpn5 and another involving Rpn2, are both important for stabilizing substrate-processing conformations. Mutations that disrupt these interactions both destabilize substrate-processing conformations relative to the substrate-accepting conformation and diminish the proteasome’s ability to successfully unfold and degrade hard-to-unfold substrates, providing a link between the proteasome’s conformational state and its unfolding ability. 

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