Case Studies of Environmental Visualization

The performance gap between simulation and reality has been identified as a major challenge to achieving sustainability in the Built Environment. While Post-Occupancy Evaluation (POE) surveys are an integral part of better understanding building performance, and thus addressing this issue, the importance of POE remains relatively unacknowledged within the wider Built Environment community. A possible reason that has been highlighted is that POE survey data is not easily understood and utilizable by non-expert stakeholders, including designers. A potential method by which to address this is the visualization method, which has well established benefits for communication of big datasets. This paper presents two case studies where EnViz (short for “Environmental Visualization”), a prototype software application developed for research purposes, was utilized and its effectiveness tested via a range of analysis tasks. The results are discussed and compared with those of previous work that utilized variations of the methods presented here. The paper concludes by presenting the lessons drawn from the five-year period of EnViz, emphasizing the potential of environmental visualization for decision support in environmental design and engineering for the built environment, and suggests directions for future development

Dynamically-Driven Enhancement of the Catalytic Machinery of the SARS 3C-Like Protease by the S284-T285-I286/A Mutations on the Extra Domain

<div><p>Previously we revealed that the extra domain of SARS 3CLpro mediated the catalysis via different mechanisms. While the R298A mutation completely abolished the dimerization, thus resulting in the inactive catalytic machinery, N214A inactivated the enzyme by altering its dynamics without significantly perturbing its structure. Here we studied another mutant with S284-T285-I286 replaced by Ala (STI/A) with a 3.6-fold activity increase and slightly enhanced dimerization. We determined its crystal structure, which still adopts the dimeric structure almost identical to that of the wild-type (WT), except for slightly tighter packing between two extra-domains. We then conducted 100-ns molecular dynamics (MD) simulations for both STI/A and WT, the longest reported so far for 3CLpro. In the simulations, two STI/A extra domains become further tightly packed, leading to a significant volume reduction of the nano-channel formed by residues from both catalytic and extra domains. The enhanced packing appears to slightly increase the dynamic stability of the N-finger and the first helix residues, which subsequently triggers the redistribution of dynamics over residues directly contacting them. This ultimately enhances the dynamical stability of the residues constituting the catalytic dyad and substrate-binding pockets. Further correlation analysis reveals that a global network of the correlated motions exists in the protease, whose components include all residues identified so far to be critical for the dimerization and catalysis. Most strikingly, the N214A mutation globally decouples this network while the STI/A mutation alters the correlation pattern. Together with previous results, the present study establishes that besides the classic structural allostery, the dynamic allostery also operates in the SARS 3CLpro, which is surprisingly able to relay the perturbations on the extra domain onto the catalytic machinery to manifest opposite catalytic effects. Our results thus imply a promising avenue to design specific inhibitors for 3CL proteases by disrupting their dynamic correlation network.</p></div

Additional file 1 of A cuproptosis score model and prognostic score model can evaluate clinical characteristics and immune microenvironment in NSCLC

Supplementary Material 1: Figure S1. (A) PCR validation of CRGs expression level among normal cell lines and NSCLC cell lines

Dynamic behavior of Asn28.

<p>Three separate time-trajectories of the Chi1 dihedral angle of Asn28 of protomer A (a-c) and protomer B (d-f) for STI/A (black) and WT (red). Three separate time-trajectories of the Chi2 dihedral angle of Asn28 of protomer A (g-i) and protomer B (j-l) for STI/A (black) and WT (red). Protomer A and B are denoted as P1 and P2 respectively.</p

Dynamic behavior of the Glu166-His172 interaction.

<p>Three separate time-trajectories of the Chi1 dihedral angle of Glu166 of protomer A (a-c) and protomer B (d-f) for STI/A (black) and WT (red). Three separate time-trajectories of the distance between Glu166 and His172 of protomer A (g-i) and protomer B (j-l) for STI/A (black) and WT (red). Protomer A and B are denoted as P1 and P2 respectively.</p

Transmission of the STI/A mutation effects on the extra domains to the catalytic machinery by the dynamically-driven allostery.

<p>(a)-(e). The cavity volumes of the nano-channel of STI/A in the first simulation at 0, 25, 50, 75 and 100 ns. (f). The crystal structure of STI/A with key residues having relevant dynamical changes displayed and labeled. The cavity is represented by the violet mesh.</p

Hydrogen Bond Occupancy for STI/A and WT with Significant Differences.

<p>Hydrogen Bond Occupancy for STI/A and WT with Significant Differences.</p

Dynamic behavior of Thr25 and Cys44.

<p>Three separate time-trajectories of Phi (a-c) and Psi (d-f) dihedral angles of Thr25 of protomer A; and Phi (g-i) and Psi (j-l) dihedral angles of Thr25 of protomer B for STI/A (black) and WT (red). Three separate time-trajectories of the distance between Thr25 and Cys44 of protomer A (m-o) and protomer B (p-r) for STI/A (black) and WT (red). Three separate time-trajectories of the volume enclosed by Thr25 and Cys44 of protomer A (s-u) and protomer B (v-x) for STI/A (black) and WT (red). Protomer A and B are denoted as P1 and P2 respectively.</p

Dynamic behavior of the catalytic dyad.

<p>Three separate time-trajectories of the distance between NE2 of His41 and SG of Cys145 atoms of protomer A (a–c) and protomer B (d-f) for STI/A (black) and WT (red). Three separate time-trajectories of the Chi2 dihedral angle of His41 of protomer A (g-i) and protomer B (j-l) for STI/A (black) and WT (red). Protomer A and B are denoted as P1 and P2 respectively.</p

Crystal structure of the STI/A mutant.

<p>(a). Overall superimposition of the dimeric STI/A (violet) and WT (cyan; PDB code of 2H2Z (18) structures. (b) Superimpositions of the catalytically critical residues of STI/A (violet) and WT (cyan; PDB code of 2H2Z (18). (c). Diagram showing the distance (d) between the mass centers of two extra domains; and the angle (Θ) by the mass centers of two extra domains as well as the mass center of two chymotrypsin folds together (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101941#s2" target="_blank">Material and Methods</a> for more details). The cavity volumes (V) of the nano-channels of STI/A (d) and WT (e) as represented by violet dots, which were calculated with the program: POVME (38).</p