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Niagara is currently the fastest supercomputer accessible to academics in Canada. It was deployed at the beginning of 2018 and has been serving the research community ever since. This homogeneous 60,000-core cluster, owned by the University of Toronto and operated by SciNet, was intended to enable large parallel jobs and has a measured performance of 3.02 petaflops, debuting at #53 in the June 2018 TOP500 list. It was designed to optimize throughput of a range of scientific codes running at scale, energy efficiency, and network and storage performance and capacity. It replaced two systems that SciNet operated for over 8 years, the Tightly Coupled System (TCS) and the General Purpose Cluster (GPC) [13]. In this paper we describe the transition process from these two systems, the procurement and deployment processes, as well as the unique features that make Niagara a one-of-a-kind machine in Canada.

As part of the mitochondrial respiratory chain, cytochrome c oxidase utilizes the energy produced by the reduction of O2 to water to fuel vectorial proton transport. The mechanism coupling proton pumping to redox chemistry is unknown. Recent advances have provided evidence that each of the four observable transitions in the complex catalytic cycle consists of a similar sequence of events. However, the physico-chemical basis underlying this recurring sequence has not been identified. We identify this recurring pattern based on a comprehensive model of the catalytic cycle derived from the analysis of oxygen chemistry and available experimental evidence. The catalytic cycle involves the periodic repetition of a sequence of three states differing in the spatial distribution of charge in the active site: [0|1], [1|0], and [1|1], where the total charge of heme a and the binuclear center appears on the left and on the right, respectively. This sequence recurs four times per turnover despite differences in the redox chemistry. This model leads to a simple, robust, and reproducible sequence of electron and proton transfer steps and rationalizes the pumping mechanism in terms of electrostatic coupling of proton translocation to redox chemistry. Continuum electrostatic calculations support the proposed mechanism and suggest an electrostatic origin for the decoupled and inactive phenotypes of ionic mutants in the principal proton-uptake pathway.

The geometry of crambin, a protein with 46 residues, was determined by ab initio HF/4-21G geometry optimization. The results are compared with the crystal structure of the compound and with HF/4-21G φ,ψconformational geometry maps calculated for the model dipeptide N-acetyl-N′-methylalaninamide. Rootmean-square (rms) deviations between calculated and crystallographic backbone structural parameters are 1.5°for N-C(R)-C′ and 0.013 and 0.017 Å, respectively, for N-C(R) and C(R)-C′. In the case of N-C(R)-C′ the rms deviations are small compared to the observed range of values, which is from <108°to >118°, confirming a definite conformational dependence of peptide backbone structural parameters on φ and ψ. In contrast, the deviations in bond lengths are of the same magnitude as the overall variations. The considerable nonplanarity of the peptide units found in the crystal structure is well reproduced by the calculations. When the calculated and crystal structures are superimposed, the rms positional deviation is 0.6 Å for the heavy atom framework and 0.4 Å for the backbone chain. The phenomenon of helix compression is confirmed that is found in elongated helical chains compared to isolated residues or smaller oligomers.

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Gramicidin is a hydrophobic peptide that assembles as a head-to-head dimer in lipid membranes to form water-filled channels selective to small monovalent cations. Two diastereoisomeric forms, respectively SS and RR, of chemically modified channels in which a dioxolane ring links the formylated N-termini of two gramicidin monomers, were shown to form ion channels. To investigate the structural basis underlying experimentally measured differences in proton conductance in the RR and SS channels, we construct atomic-resolution models of dioxolane-linked gramicidin dimers by analogy with the native dimer. A parametric description of the linker compatible with the CHARMM force field used for the peptide is derived by fitting geometry, vibrational frequencies, and energy to the results of ab initio calculations. The linker region of the modified gramicidin dimers is subjected to an extensive conformational search using high-temperature simulated annealing, and free-energy surfaces underlying the structural fluctuations of the channel backbone at 298K are computed from molecular dynamics simulations. The overall secondary structure of the beta-helical gramicidin pore is retained in both linked channels. The SS channel is found in a single conformation resembling that of the native dimer, with its peptide bonds undergoing rapid librations with respect to the channel axis. By contrast, its RR counterpart is characterized by local backbone distortions in which the two peptide bonds flanking the linker are markedly tilted in order to satisfy the pitch of the helix. In these distorted structures, each of the two carbonyl groups points either in or out of the lumen. Flipping these two peptides in and out involves thermally activated transitions, which results in four distinct conformational states at equilibrium with one another on a nanosecond time scale. This work opens the way to detailed comparative studies of structure-function relationships in biological proton ducts.

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