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Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculatein silicochromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM. 

Abstract. Chronologies of glacier deposits in the Transantarctic Mountains provide important constraints on grounding-line retreat during the last deglaciation in the Ross Sea. However, between Beardmore Glacier and Ross Island – a distance of some 600 km – the existing chronologies are generally sparse and far from the modern grounding line, leaving the past dynamics of this vast region largely unconstrained. We present exposure ages of glacial deposits at three locations alongside the Darwin–Hatherton Glacier System – including within 10 km of the modern grounding line – that record several hundred meters of Late Pleistocene to Early Holocene thickening relative to present. As the ice sheet grounding line in the Ross Sea retreated, Hatherton Glacier thinned steadily from about 9 until about 3 ka. Our data are equivocal about the maximum thickness and Mid-Holocene to Early Holocene history at the mouth of Darwin Glacier, allowing for two conflicting deglaciation scenarios: (1) ∼500 m of thinning from 9 to 3 ka, similar to Hatherton Glacier, or (2) ∼950 m of thinning, with a rapid pulse of ∼600 m thinning at around 5 ka. We test these two scenarios using a 1.5-dimensional flowband model, forced by ice thickness changes at the mouth of Darwin Glacier and evaluated by fit to the chronology of deposits at Hatherton Glacier. The constraints from Hatherton Glacier are consistent with the interpretation that the mouth of Darwin Glacier thinned steadily by ∼500 m from 9 to 3 ka. Rapid pulses of thinning at the mouth of Darwin Glacier are ruled out by the data at Hatherton Glacier. This contrasts with some of the available records from the mouths of other outlet glaciers in the Transantarctic Mountains, many of which thinned by hundreds of meters over roughly a 1000-year period in the Early Holocene. The deglaciation histories of Darwin and Hatherton glaciers are best matched by a steady decrease in catchment area through the Holocene, suggesting that Byrd and/or Mulock glaciers may have captured roughly half of the catchment area of Darwin and Hatherton glaciers during the last deglaciation. An ensemble of three-dimensional ice sheet model simulations suggest that Darwin and Hatherton glaciers are strongly buttressed by convergent flow with ice from neighboring Byrd and Mulock glaciers, and by lateral drag past Minna Bluff, which could have led to a pattern of retreat distinct from other glaciers throughout the Transantarctic Mountains. 

Abstract. We report cosmogenic-nuclide measurements from two isolated groups of nunataks in West Antarctica: the Pirrit Hills, located midway between the grounding line and the divide in the Weddell Sea sector, and the Whitmore Mountains, located along the Ross–Weddell divide. At the Pirrit Hills, evidence of glacial-stage ice cover extends ∼320 m above the present ice surface. Subsequent thinning mostly occurred after ∼14 kyr BP, and modern ice levels were established some time after ∼4 kyr BP. We infer that, like at other flank sites, these changes were primarily controlled by the position of the grounding line downstream. At the Whitmore Mountains, cosmogenic 14C concentrations in bedrock surfaces demonstrate that ice there was no more than ∼190 m thicker than present during the past ∼30 kyr. Combined with other constraints from West Antarctica, the 14C data imply that the divide was thicker than present for a period of less than ∼8 kyr within the past ∼15 kyr. These results are consistent with the hypothesis that the divide initially thickened due to the deglacial rise in snowfall and subsequently thinned in response to retreat of the ice-sheet margin. We use these data to evaluate several recently published ice-sheet models at the Pirrit Hills and Whitmore Mountains. Most of the models we consider do not match the observed timing and/or magnitude of thickness change at these sites. However, one model performs relatively well at both sites, which may, in part, be due to the fact that it was calibrated with geological observations of ice-thickness change from other sites in Antarctica. 

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike’s full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems.