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862 Annual Review of Ecology and Systematics 21: 423–447. 863 864 Charnov, E.L., and W.M. Schaffer. 1973. Life-history consequences of natural selection: Cole’s result 865 revisited. The American Naturalist 107: 791–793. 866 867 Chave, J., D.A. Coomes, S. Jansen, S.L. Lewis, N.G. Swenson, and A.E. Zanne. 2009. Towards ...
It is made doi: https://doi.org/10.1101/2021.02.17.431656 ; this version posted February 17, 2021. The copyright holder for this preprint available under a CC-BY-NC-ND 4.0 International license . 36 909 Friedman, J., and M.J. Rubin. 2015. All in good time: Understanding annual and perennial strategies in 910 plants. Am...
952 953 Grotkopp, E., M. Rejmánek, and T.L. Rost. 2002. Toward a causal explanation of plant invasiveness: 954 Seedling growth and life-history strategies of 29 pine (Pinus) species. American Naturalist 159: 396–419. 955 956 Grime, J.P. 1977. Evidence for the existence of three primary strategies in plants and its rele...
USDA Forest Service General Technical Report INT-GTR-313, Intermountain Research 990 Station, Provo, Utah, USA. 991 992 Kleyer, M., J. Trinogga, M.A. Cebrián, R. Ejrnæs, A. Trenkamp, C. Fløjgaard, D.C. Albach, et al. 2019. 993 Trait correlation network analysis identifies biomass allocation traits and stem specific len...
Journal of Ecology 92: 1033 384–396. 1034 1035 Morishima, H., Y. Sano, and H.I. Oka. 1984. Differentiation of perennial and annual types due to habitat 1036 conditions in the wild rice Oryza perennis. Plant Systematics and Evolution 144: 119–135. bioRxiv preprint (which was not certified by peer review) is the author/f...
American Naturalist 176: 1073 E152–E161. 1074 1075 Reich, P.B. 2014. The world-wide “fast-slow” plant economics spectrum: A traits manifesto. Journal of 1076 Ecology 102: 275–301. 1077 1078 Reynolds, L.K., J.J. Stachowicz, A.R. Hughes, S.J. Kamel, B.S. Ort, and R.K. Grosberg. 2017. Temporal 1079 stability in patterns o...
It is made doi: https://doi.org/10.1101/2021.02.17.431656 ; this version posted February 17, 2021. The copyright holder for this preprint available under a CC-BY-NC-ND 4.0 International license . 44 1114 Singmann, H., B. Bolker, J. Westfall, F. Aust, and M.S. Ben-Shachar. 2020. afex: Analysis of factorial 1115 experime...
Van Tassel. 2020. Balancing 1154 forage production, seed yield, and pest management in the perennial sunflower Silphium integrifolium 1155 (Asteraceae). Agronomy 10: 1471. 1156 1157 Vu, V.Q. 2011. ggbiplot: A ggplot2 based biplot. R package version 0.55. http://github.com/vqv/ggbiplot 1158 1159 Ward, P.R., J.A. Palta, ...
I t i s m a d e b o R x v p r e p r i n t d o i : i i h t t p s : / / d o i . o r g / 1 0 . 1 1 0 1 / 2 0 2 1 . 0 2 . 1 7 . 4 3 1 6 5 6 ; t h s i v e r s o n i p o s t e d F e b r u a r y 1 7 , 2 0 2 1 . T h e c o p y r i g h t h o d e r l f o r t h s i p r e p r i n t P. leptostachyus 4 52 (39-68) 4 46 (34-60) 4 P. m...
T h e c o p y r i g h t h o d e r l f o r t h s i p r e p r i n t Table 2. Analysis of variance (ANOVA) table of the final, reduced linear mixed models for the full dataset, including accession-level principal components (Figure 1) and seed, germination, and vegetative growth traits. Trait Genus Life span Genus × Life...
ANOVAs are all type III with the exception of PC1, PC2, seed mass, and germination proportion (type I), due to the data consisting of only accession-level means with no significant random effects. Additional random effect significance is listed in Appendix S9. Significant values are bolded (at least P < 0.05). When non...
o r g / 1 0 . 1 1 0 1 / 2 0 2 1 . 0 2 . 1 7 . 4 3 1 6 5 6 ; t h s i v e r s o n i p o s t e d F e b r u a r y 1 7 , 2 0 2 1 . T h e c o p y r i g h t h o d e r l f o r t h s i p r e p r i n t bioRxiv preprint doi: https://doi.org/10.1101/2021.02.17.431656 ; this version posted February 17, 2021. The copyright holder f...
Correlation networks for (A) the full dataset, and the dataset subgroups: (B) annuals, (C) perennials, (D) Lathyrus, (E) Phaseolus, and (F) Vicia. Presence of lines (edges) between trait nodes indicates a significant correlation between those traits (Pearson; P < 0.05). Blue signifies a positive correlation and red a n...
bioRxiv preprint doi: https://doi.org/10.1101/2021.08.20.457167 ; this version posted August 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Evolving a generalist biosensor for bicyclic monoterpenes...
Although monoterpenes are traditionally sourced from plants, microbes are being increasingly engineered to provide a more reliable, pure and space-efficient means of production2, typically via heterologous expression of a pathway for the production of the common intermediate geranyl pyrophosphate (GPP) followed by a spec...
The Pcamr promoter was extracted from the natural P. putida CamR-bearing plasmid (GenBank: D14680.1), and included a portion protected by CamR in a DNase footprinting assay15 upstream from the self-cleaving ribozyme PlmJ16. To test the function of the heterologous Pcamr/CamR system in E. coli, CamR was constitutively e...
To improve the performance of the circuit for resolving differences between and improvements with new, relatively inactive effector molecules, the dynamic range of the reporter system was systematically 4 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.20.457167 ; this version posted August 21, 2021. The copyright...
All rights reserved. No reuse allowed without permission. engineering of strains to produce terpene products. We therefore leveraged a previously developed directed evolution approach, Seamless Enrichment of Ligand-Inducible Sensors (SELIS22, (Supplementary Figure 2), to improve the responsivity of CamR towards the ter...
We therefore cloned all 30 unique single amino acid substitutions that were recovered from CamR evolution and screened them for activity against camphor, borneol, fenchol, eucalyptol, and camphene (Figure 3b, Supplementary Figure 3). As might have been expected based on the selection data alone, the three substitutions...
Indeed, screening each final CamR generation against camphor, borneol, fenchol, eucalyptol, and camphene revealed that the later, fenchol-targeted generations had nonetheless become more broadly activated by all tested terpenes (Figure 4c, Supplementary Figure 7). Beyond these five monoterpenes, the final CamR generation,...
Thus, there may just be more ‘handles’ for the effector binding site to recognize and distinguish for the BIAs, than for the monoterpenes. In this regard, it is interesting to note that the closest thing to a specialist that has appeared in nature or directed evolution is camphor-mediated activation of CamR itself, poss...
All rights reserved. No reuse allowed without permission. evolution, and orthogonality assays unless specifically noted. LB + 1.5% agar (BD, Franklin Lakes, NJ, USA) plates were used for routine cloning and directed evolution. The plasmids described in this work were constructed using Gibson assembly, golden gate assemb...
Biosensor response measurement For performing a biosensor response assay, the pCamR and pPcamr-RFP plasmids were co-transformed into DH10B cells and plated on an LB agar plate with appropriate antibiotics. Three separate colonies were picked for each transformation and were grown overnight. The following day, 20 μL of ...
Three hundred μL of this mixture was then plated across three LB agar plates containing carbenicillin, chloramphenicol and the target monoterpene dissolved in DMSO. Plates were incubated overnight at 37 °C. The following day the brightest colonies were picked and grown overnight in 1 mL of LB media containing appropria...
The resulting cultures were then assayed, as described in “Biosensor response measurement”, using seven 14 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.20.457167 ; this version posted August 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rig...
Black arrows indicate the location of the inverted repeat. (c) Dose response function of the CamR biosensor system with the native promoter (tatgct) and the modified promoter (tatAct). EC50 values are listed and color coded (blue: tatAct, pink: tatgct) (d) Response of the CamR system to a panel of monoterpenes. All cult...
(c) Response of each CamR generation to 1 mM of camphor, borneol, fenchol, eucalyptol, and camphene. (d) Fluorescent response of FEN3 to a panel of monoterpenes. All cultures were grown in the presence of 1% DMSO and fluorescence values are the averages of three biological replicates for panels b, c, and d. 20 bioRxiv ...
Production of jet fuel precursor monoterpenoids from engineered Escherichia coli. Biotechnol. Bioeng. 114, 1703–1712 (2017). 15. Aramaki, H., Sagara, Y., Hosoi, M. & Horiuchi, T. Evidence for autoregulation of camR, which encodes a repressor for the cytochrome P-450cam hydroxylase operon on the Pseudomonas putida CAM p...
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.08.451613 ; this version posted July 9, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Transcranial ph...
The analysis on receiver operating characteristic curves and multivariate data analysis also agreed with the results above. This study shows that a hand-held transcranial PA neuroimaging can detect a regional thrombotic stroke in cerebral cortex of a neonatal piglet. In particular, we conclude that the HbO2 saturation ...
Photoacoustic (PA) sensing modality, a combination of ultrasound and optical modalities, has been highlighted recently due to its high spatiotemporal resolution and deep imaging depth, which may play an alternative role for the unmet clinical need. The technology emits the pulse laser light on intact skin, and the ligh...
On the other hand, the photothrombosis (PTS) stroke model induces ischemia in a well-defined region, with minimal surgical intervention, low mortality, and high reproducibility [34]. The PTS technique induces a cortical infarction through the photo- activation of a light-sensitive dye (e.g., Rose bengal, erythrosin B) ...
Figure 1c shows a representative TTC image, illustrating clear development of infarction via PTS technique. Dotted circles indicate the candidate PTS regions, and blue and white colors indicate the affected and control regions-of-interest (ROIs). Apparent regional developments of cerebral infarction were identified at ...
Finally, we analyzed the pooled data to have a generalized perspective how accurate PA imaging can detect PTS lesions (Figure 2a). The HbO2 saturation again yielded strong statistical significance: 58.40 ± 11.86% vs. 28.33 ± 13.08% in control and affected ROIs, respectively. Notably, HbO2 quantity presented a statistic...
The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. the ROC curves of the cases with a single-lesion (n = 5) and two-lesions (n = 12), respectively. The blue line presents the ROC curve using the pooled data (n =...
However, the tissue quantity of total hemoglobin did not provide additional effectiveness in the context of the PTS model. There are many foreseeable variables in hemoglobin quantity; for example, inconsistent distance and angle of the PA probe from the fetal head would affect light fluence and acoustic attenuation. Th...
The spatial resolution of the transcranial PA imaging is subject to the degree of phase aberration when imaging through skull layers, having heterogenous thickness with sound propagation speeds significantly different from that of soft biological tissue (4,080 m/s vs. 1,540 m/s). Even though the human newborn skull is ...
The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ischemia, has great potential for advancing clinical trials of neonatal stroke, along with promising technological progresses [47,48]. In conclusion, a transcra...
The light interaction with the dye generates free radicals that damage the endothelium sufficiently to activate platelets and produce a thrombus. During the light illumination, 1 ml sterile saline solution was perfused on the thinned skull every 5 minutes to prevent overheating and damage on target surface. No signs of...
The HbO2 saturation and tHb were decomposed from spectral PA data (700–900 nm in 10 nm interval), and transverse planes were projected in axial direction at every 1 mm depth interval. From the data, spectral unmixing was conducted by a constrained linear least-squares problem solver in MATLAB software (Mathworks Inc., ...
The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. [11] Adami R R, Grundy M E, Poretti A, Felling R J, Lemmon M and Graham E M 2016 Distinguishing Arterial Ischemic Stroke From Hypoxic–Ischemic Encephalopathy in...
All rights reserved. No reuse allowed without permission. [24] Kang J, Boctor E M, Adams S, Kulikowicz E, Zhang H K, Koehler R C and Graham E M 2018 Validation of noninvasive photoacoustic measurements of sagittal sinus oxyhemoglobin saturation in hypoxic neonatal piglets J Appl Physiol 125 983–9 [25] Kang J, Koehler R...
All rights reserved. No reuse allowed without permission. [37] Powers W J, Grubb R L, Darriet D and Raichle M E 1985 Cerebral Blood Flow and Cerebral Metabolic Rate of Oxygen Requirements for Cerebral Function and Viability in Humans J Cereb Blood Flow Metabolism 5 600–8 [38] Wang L V 2008 Prospects of photoacoustic to...
Pooled data (n = 17 from 11 animals) Control Affected p HbO2 saturation (%) 58.40 ± 11.86 28.33 ± 13.08 < 0.0001 (****) Total Hb (tHb) concentration (a.u.) 5.83 ± 3.04 4.44 ± 2.10 0.0733 HbO2 concentration (a.u.) 4.46 ± 2.46 2.72 ± 1.61 0.0066 (*) HbR concentration (a.u.) 1.38 ± 1.02 1.71 ± 0.70 0.2314 (p = 0.0118 when...
Blue and white dotted circles indicate the PTS lesions and control regions-of-interest. (d) Representative transverse planes of HbO2 saturation, total hemoglobin (tHb) overlaid on the TTC image. (e) Corresponding transverse maps of HbO2 and HbR quantities. Black bars indicate 1 cm. Asterisk marks indicate the cortical ...
Threshold (a.u.) Threshold (a.u.) Figure 3. Sensitivity, specificity, and accuracy to classify the photothrombotic (PTS) lesions for the varying threshold values. (a) HbO2 saturation, (b) total hemoglobin (tHb), and (c) oxy- and deoxyhemoglobin (HbO2 and HbR) in pooled, single-lesion, and two-lesion groups. Solid and d...
5 10 15 20 25 30 35 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.31.458325 ; this version posted August 31, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available u...
We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation. Engineering of ACE2 N-glycosylation by site- directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization withou...
While this provided unprecedented insight into the protein-protein interactions between Spike and ACE2, the structural impact of protein-bound glycans on the Spike-ACE2 interface could not be assessed experimentally so far due to their compositional diversity and conformational flexibility. Here, in silico modeling of ...
To assess the impact of all seven individual N-glycosylation sites of hACE2 on its interaction with Spike, we first elucidated the entire glycome of rshACE2 (Fig. S1). This also 4 115 120 125 130 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.31.458325 ; this version posted August 31, 2021. The copyright holder...
2a and Fig. S4. Further analysis showed that glycans at N122, N165 and N343 on Spike directly interact with ACE2 or its glycans (Fig. 1b, c, Fig. 2b, c). It has been reported that Spike mutants lacking the glycans at N331 and N343 display reduced infectivity, while elimination of the glycosylation motif at N234 results...
S5 for monomers 1 and 2). Since our modeling clearly confirmed that ACE2 glycosylation plays a significant role in its binding to Spike (Fig. 1d,e), we also determined the area of the Spike-ACE2 interface region, by subtracting the SASA of the complex from the SASA of the individual proteins and dividing by two. The to...
These glycans have been implicated as being relevant for binding before,21, as well as the glycan at N53,35 but no conclusions were drawn if they contribute positively or negatively to binding. Mehdipour and Hummer predicted the glycan at N322 to contribute favorably to binding, because of the favorable interactions of...
Three thermal transitions could be discriminated. The first midpoint of transition (Tm1) is due to the unfolding of ACE2, whereas 9 235 240 245 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.31.458325 ; this version posted August 31, 2021. The copyright holder for this preprint (which was not certified by peer ...
Plots of kobs (observed association rate) as a function of Spike concentration were generated by fitting the association data to a 1:1 binding model. Binding analysis was performed by dipping ACE2-loaded biosensors into 2-fold serial dilutions of purified Spike (1.6-50 nM). All measurements were performed in triplicate...
The viral RNA content of the culture supernatants was quantified by RT-qPCR and expressed as fold change reduction relative to untreated controls. Data are presented as mean ± SEM of 2-3 independent experiments each performed in triplicates. Deglyco-ACE2-wt-Fc, enzymatically deglycosylated wild- type ACE2-Fc; desialo-A...
The results presented above uncover the critical importance of N-glycans located at the ACE2- Spike interface for the infection of host cells by SARS-CoV-2. This prompted us to test the feasibility of removing all N-glycans from clinical-grade rshACE2, which has undergone placebo-controlled phase 2 clinical testing in ...
The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . activities of ACE2-T92Q-Fc, ACE2-N322Q-Fc and ACE2-T92Q-N322Q-Fc were found to ...
It is made available under a CC-BY-ND 4.0 International license . based SARS-CoV-2 neutralization assays. It is of note that the moderately enhanced affinity of ACE2 glycovariants for monomeric RBD observed in biolayer interferometry experiments relates to a far more pronounced increase of their virus-neutralization po...
It is made available under a CC-BY-ND 4.0 International license . as compared to transduction with wild-type ACE2.38 This was attributed to the much lower cellular content of the mutant protein relative to the native enzyme, thus demonstrating that the importance of N-glycosylation for proper folding of glycoproteins d...
The entire glycan trees were clustered based on the conformations of the individual glycosidic linkages.43 This resulted in conformational bundles containing 1301, 1340 and 2413 distinct conformations of Man5, Man9 and NaNaF, respectively. These conformations were fitted onto the respective glycosylation site in the Sp...
A hydrogen bond was logged if the donor-acceptor distance is within 0.25 nm and the donor- hydrogen-acceptor angle was larger than 135 degrees. The solvent-accessible surface area was determined by rolling a probe with diameter 0.14 nm over the surface of the protein, using slices of 0.005 nm width. An atom contact was...
Soluble proteins were harvested after 120-144 h by centrifugation (10 000 g, 15 min, 4°C). Purification of recombinantly expressed proteins μ After filtration through 0.45 m membrane filters (Merck Millipore, Germany), supernatants containing RBD or soluble Spike were concentrated and diafiltrated against 20 mM sodium ...
Biotinylated proteins were further purified using PD-10 desalting columns (Cytiva) according to the manufacturer’s protocol. All assays were conducted in PBS supplemented with 0.05% (v/v) Tween 20 and 0.1% (w/v) BSA (PBST-BSA) at 25°C with the plate shaking at 1000 rpm. The SAX biosensors were first equilibrated in PBS...
Analyses were performed on an LC20 Prominence HPLC equipped with a refractive index detector RID- 24 575 580 585 590 595 600 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.31.458325 ; this version posted August 31, 2021. The copyright holder for this preprint (which was not certified by peer review) is the auth...
The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . in HPLC-grade water) to 65% eluent B (80% acetonitrile in 80 mM ammonium format...
It is made available under a CC-BY-ND 4.0 International license . Subsequently, cells were washed two times with MEM to remove unadsorbed virus. After incubation for 24 h at 37°C in MEM supplemented with 2% FBS, viral RNA was extracted from the culture supernatant using the QiaAmp Viral RNA Minikit (Qiagen, Germany), a...
Transfection-grade pCAGGS plasmids were provided by Rainer Hahn and Gerald Striedner (University of Natural Resources and Life Sciences Vienna, Austria) in the framework of the BOKU COVID-19 Initiative. The authors thank Irene Schaffner and Jakob Wallner (BOKU Core Facility Biomolecular & Cellular Analysis) for assisti...
Competing interests J.M.P. declares a conflict of interest as a founder, supervisory board member, and shareholder of Apeiron Biologics. J.N. and G.W. are employees of Apeiron Biologics. Apeiron holds a patent on the use of ACE2 for the treatment of lung, heart, or kidney injury and applied for a patent to treat COVID-...
(2020) Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir Med 8, 1154-1158. doi: 10.1016/S2213-2600(20)30418-5 Barnes, C. O., Jette, C. A., Abernathy, M. E., Dam, K. A., Esswein, S. R., Gristick, H. B., Malyutin, A. G., Sharaf, N. G., Huey-Tubman, K. E., Lee, Y. E., Robbiani, D. F., Nussenzweig, M. C., We...
Proc Natl Acad Sci U S A 117, 28046-28055. doi: 10.1073/pnas.2016093117 Chan, K. K., Dorosky, D., Sharma, P., Abbasi, S. A., Dye, J. M., Kranz, D. M., Herbert, A. S., and Procko, E. (2020) Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 369, 1261-1265. doi: 10.1126/science...
Proteins 89, 1134-1144. doi: 10.1002/prot.26086 Yang, Q., Hughes, T. A., Kelkar, A., Yu, X., Cheng, K., Park, S., Huang, W. C., Lovell, J. F., and Neelamegham, S. (2020) Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration. Elife 9. doi: 10.7554/eLife.61552 Allen, J. D., Watanabe, Y., Chawla, ...
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Journal of Computer-Aided Molecular Design 8, 695 - 708. doi: 10.1007/Bf00124016 Peric-Hassler, L., Hansen, H. S., Baron, R., and Hünenberger, P. H. (2010) Conformational properties of glycose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling. Carbohydrate rese...
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bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 I...
We expect that our RPnet holds promise in analyzing conformational dynamics of biological macromolecules. 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has...
In another Bayesian kinetic lumping algorithm, a Gibbs sampling algorithm is applied to facilitate the search of the optimal kinetic lumping.40 Methods that explicitly considers the possible transition paths in the microstate transition matrix also exists, an example of which is the Most Probable Path (MPP) lumping alg...
the eigenvectors of the microstate TPM) and a backward projected vector of macrostate eigenvectors is adopted as the scoring function for evaluation. In the RPnet, this eigenvector-based scoring function is used as the loss function, and the optimization of this loss function would improve the matching of dynamics betw...
Eq. (5) is straightforwardly obtained as (cid:5) is related by summing up all the equilibrium identity matrix, following the fact that populations within the corresponding macrostates. We will then examine the “evolution of , respectively). Under the population” at microstate and macrostate level ( times Markovian cond...
We note that the “lumping” process can be viewed as a projection, by making use of the projection operator framework that was previously developed by Szabo and Hummer.48 (cid:6)(cid:7)(cid:10)(cid:0), (cid:13) (cid:26) (cid:7) (cid:17) (cid:12) (cid:10)(cid:17) (cid:28) (cid:7) 1 (cid:29) (cid:26) ( 9 ) (cid:17) (cid:4...
1c), the reverse-projected modes (Red curves in right panels of Fig. 1c) largely deviate from the original transition modes. In addition, when we examine closely the reverse projected modes (green lines in Fig. 1b and red lines in Fig. 1c), we notice the reverse-projected modes are “continuous” within each macrostate r...
reverse projected transition modes and the original microstate transition modes. and . (cid:9) and . Basically, )(cid:20)(cid:21)(cid:22)(cid:23)(cid:24)(cid:2)#(cid:4)(cid:0)(cid:10)(cid:0) 7 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder for...
The output of each network is a macrostates. The output is also used to compute the macrostate TCM. 1 0 ! ! vector, representing the membership of the input microstate to the 8 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder for this preprint (...
And the eigenvectors value decomposition procedure and the update is done using the PyTorch functionality.53,54 Scaling and normalization have been done in the singular value decomposition (SVD) step to ensure the eigenvectors of original microstates and reverse projected ones are of the same scale. More details could ...
A velocity-Verlet integrator55 prevent the particle from diffusing out of the region: coupled with Andersen thermostat56 (T=1, collision frequency = 5 per time unit) was adopted for the NVT simulation. The integration time step is 0.001 time unit, and the trajectories is saved every 100 steps. As a result, our 109-step...
These batch sizes are chosen by preliminary scanning through the batch sizes ranging from 1000 to 10000, and the tests showed that if the batch sizes are too small or too large, the network might be much harder to converge. 6. Assessing the quality of the lumped models To compute the GMRQ and metastability of the lumpi...
FIG. 3. Performance of RPnet on the alanine dipeptide system. (a) The Ramachandran plot of the alanine dipeptide. (b-e) Lumping results by 4 different algorithms. (b) PCCA+. (c) RPnet. 13 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder for this...
4(e), the lumped model from RPnet results in higher GMRQ and metastability, indicating that the macrostate model obtained from RPnet is better than that of PCCA+. These observations suggest that PCCA+ could suffer from the instability of eigenvector components and thus generate fuzzy state boundaries and leads to lower...
The Clamp open/close angles are also presented in the snapshots of metastable states. (b-e) Lumping results at lagtime 90 ns for (b) PCCA+, (c) RPnet, (d) Hierarchical clustering with Ward linkage, and (e) MPP. (f) Evolution of the Y-loss of RPnet over 30 epochs, with referenced to the Y-loss of the other three lumping...
In contrast, algorithms that are based on eigen- decompositions of TPMs (e.g. PCCA+) may become more sensitive to numerical instabilities under those conditions (e.g. in the 2D-potential example in Fig. 4, see also Fig S3 for the analysis on robustness). Our design of the loss function is inspired by a previously devel...
Using our proposed Y-loss based on the reverse projection scheme, we have also set up a neural network that allows an automatic optimization of lumping. Combining the two parts, we have obtained our RPnet framework, that allows an automatic method that can give rise to physically sound lumping. As demonstrated by the t...
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This (cid:12)(cid:13), which can be written as , therefore (cid:10)(cid:11)(cid:15)(cid:7)(cid:17) (cid:15)(cid:17) (cid:8) (cid:9) . Then we will have, (cid:15)(cid:17) (cid:15)(cid:17) (cid:10)(cid:11)(cid:15)(cid:7) (cid:9) (cid:13) (cid:9) (cid:13)(cid:14) (cid:9) (cid:13)(cid:21)(cid:18) (cid:22) (cid:13)(cid:23) ...
(S4) (cid:13)(cid:28)(cid:21)(cid:29)(cid:23) (cid:9) (cid:13)(cid:28)(cid:21)(cid:29)(cid:23)(cid:13) 21 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has g...
(cid:21)3(cid:26) (cid:15) 3(cid:15)(cid:17)(cid:19). (cid:21) (S9) 3(cid:7)3 (cid:9) (cid:15)(cid:17)(cid:19). (cid:21) ( (cid:17)(cid:19). (cid:21) (cid:9) (cid:15)(cid:30) (cid:9) (cid:18) 22 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.04.455071 ; this version posted August 6, 2021. The copyright holder f...
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.16.154187 ; this version posted June 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ppGpp is a bacterial...
The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Results Control of ppGpp synthesis and hydrolysis To study the relation between ppGpp and cell growth and division, two enzymes were used: the catalytic domain ...