The Green Center for Systems Biology

Research Output 1991 2019

2019

A fully-automated, robust, and versatile algorithm for long-term budding yeast segmentation and tracking

Ezgi Wood, N. & Doncic, A., Mar 1 2019, In : PloS one. 14, 3, e0206395.

Research output: Contribution to journalArticle

Open Access
Saccharomycetales
Yeast
yeasts
cells
Imaging techniques

A Two-Enzyme Adaptive Unit within Bacterial Folate Metabolism

Schober, A. F., Mathis, A. D., Ingle, C., Park, J. O., Chen, L., Rabinowitz, J. D., Junier, I., Rivoire, O. & Reynolds, K. A., Jun 11 2019, In : Cell Reports. 27, 11, p. 3359-3370.e7

Research output: Contribution to journalArticle

Open Access
Folic Acid
Metabolism
Tetrahydrofolate Dehydrogenase
Thymidylate Synthase
Enzymes

High-Order Epistasis in Catalytic Power of Dihydrofolate Reductase Gives Rise to a Rugged Fitness Landscape in the Presence of Trimethoprim Selection

Tamer, Y. T., Gaszek, I. K., Abdizadeh, H., Batur, T. A., Reynolds, K. A., Atilgan, A. R., Atilgan, C. & Toprak, E., Jul 1 2019, In : Molecular biology and evolution. 36, 7, p. 1533-1550 18 p.

Research output: Contribution to journalArticle

Open Access
dihydrofolate reductase
epistasis
Tetrahydrofolate Dehydrogenase
Trimethoprim
trimethoprim

Non-antibiotic Small-Molecule Regulation of DHFR-Based Destabilizing Domains In Vivo

Peng, H., Chau, V. Q., Phetsang, W., Sebastian, R. M., Stone, M. R. L., Datta, S., Renwick, M., Tamer, Y. T., Toprak, E., Koh, A., Blaskovich, M. A. T. & Hulleman, J. D., Dec 13 2019, In : Molecular Therapy - Methods and Clinical Development. 15, p. 27-39 13 p.

Research output: Contribution to journalArticle

Open Access
Tetrahydrofolate Dehydrogenase
Trimethoprim
Blood-Retinal Barrier
Proteins
Microbial Drug Resistance

Rapid ultrasensitive detection platform for antimicrobial susceptibility testing

Cansizoglu, M. F., Tamer, Y. T., Farid, M., Koh, A. & Toprak, E., May 1 2019, In : PLoS biology. 17, 5, p. e3000291

Research output: Contribution to journalArticle

Open Access
detectors
anti-infective agents
Anti-Bacterial Agents
Detectors
antibiotics

Tau local structure shields an amyloid-forming motif and controls aggregation propensity

Chen, D., Drombosky, K. W., Hou, Z., Sari, L., Kashmer, O. M., Ryder, B. D., Perez, V. A., Woodard, D. N. R., Lin, M. M., Diamond, M. I. & Joachimiak, L. A., Dec 1 2019, In : Nature communications. 10, 1, 2493.

Research output: Contribution to journalArticle

Open Access
Tauopathies
Disease control
tau Proteins
Amino Acid Motifs
HEK293 Cells
2018
8 Citations (Scopus)

An evolutionary hotspot defines functional differences between CRYPTOCHROMES

Rosensweig, C., Reynolds, K. A., Gao, P., Laothamatas, I., Shan, Y., Ranganathan, R., Takahashi, J. S. & Green, C. B., Dec 1 2018, In : Nature Communications. 9, 1, 1138.

Research output: Contribution to journalArticle

Circadian Clocks
clocks
Sequence Analysis
Clocks
Mutation
9 Citations (Scopus)

A Precise Cdk Activity Threshold Determines Passage through the Restriction Point

Schwarz, C., Johnson, A., Kõivomägi, M., Zatulovskiy, E., Kravitz, C. J., Doncic, A. & Skotheim, J. M., Jan 18 2018, In : Molecular Cell. 69, 2, p. 253-264.e5

Research output: Contribution to journalArticle

Intercellular Signaling Peptides and Proteins
Cell Cycle
Fibroblasts
Cell Line
Proteins
3 Citations (Scopus)

A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast

Moretto, F., Wood, N. E., Kelly, G., Doncic, A. & Van Werven, F. J., Dec 1 2018, In : Nature Communications. 9, 1, 780.

Research output: Contribution to journalArticle

Long Noncoding RNA
yeast
regulators
Yeast
Yeasts

A simplified mechanism for anisotropic constriction in Drosophila mesoderm

Doubrovinski, K., Tchoufag, J. & Mandadapu, K., Dec 10 2018, In : Development (Cambridge, England). 145, 24

Research output: Contribution to journalArticle

Gastrulation
Anisotropy
Mesoderm
Constriction
Drosophila
10 Citations (Scopus)

Cheminformatic Insight into the Differences between Terrestrial and Marine Originated Natural Products

Shang, J., Hu, B., Wang, J., Zhu, F., Kang, Y., Li, D., Sun, H., Kong, D. X. & Hou, T., Jun 25 2018, In : Journal of Chemical Information and Modeling. 58, 6, p. 1182-1193 12 p.

Research output: Contribution to journalArticle

Biological Products
Scaffolds
drug
Atoms
Bromine
12 Citations (Scopus)

Coevolution-based inference of amino acid interactions underlying protein function

Salinas, V. H. & Ranganathan, R., Jul 19 2018, In : eLife. 7, e34300.

Research output: Contribution to journalArticle

Amino Acids
Proteins
Benchmarking
Sequence Analysis
Technology
5 Citations (Scopus)

Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation

Bian, Y. M., He, X. B., Jing, Y. K., Wang, L. R., Wang, J. M. & Xie, X. Q., Jan 1 2018, (Accepted/In press) In : Acta Pharmacologica Sinica.

Research output: Contribution to journalArticle

Cannabidiol
Knowledge Bases
Computer Simulation
Pharmacology
delta Opioid Receptor
14 Citations (Scopus)

Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective Antagonist EMPA

Suno, R., Kimura, K. T., Nakane, T., Yamashita, K., Wang, J., Fujiwara, T., Yamanaka, Y., Im, D., Horita, S., Tsujimoto, H., Tawaramoto, M. S., Hirokawa, T., Nango, E., Tono, K., Kameshima, T., Hatsui, T., Joti, Y., Yabashi, M., Shimamoto, K., Yamamoto, M. & 4 others, Rosenbaum, D. M., Iwata, S., Shimamura, T. & Kobayashi, T., Jan 2 2018, In : Structure. 26, 1, p. 7-19.e5

Research output: Contribution to journalArticle

Orexin Receptors
Synchrotrons
Molecular Dynamics Simulation
Dissociative Disorders
Crystallography
3 Citations (Scopus)

Engineering allosteric regulation in protein kinases

Pincus, D., Pandey, J. P., Feder, Z. A., Creixell, P., Resnekov, O. & Reynolds, K. A., Nov 6 2018, In : Science Signaling. 11, 555, eaar3250.

Research output: Contribution to journalArticle

Allosteric Regulation
Yeast
Protein Kinases
Yeasts
Phosphotransferases
3 Citations (Scopus)

Hierarchical Organization Endows the Kinase Domain with Regulatory Plasticity

Creixell, P., Pandey, J. P., Palmeri, A., Bhattacharyya, M., Creixell, M., Ranganathan, R., Pincus, D. & Yaffe, M. B., Oct 24 2018, In : Cell Systems. 7, 4, p. 371-383.e4

Research output: Contribution to journalArticle

Phosphotransferases
Substrate Specificity
Catalytic Domain
Signal Transduction
Pharmacology
4 Citations (Scopus)

Integration of Multiple Metabolic Signals Determines Cell Fate Prior to Commitment

Argüello-Miranda, O., Liu, Y., Wood, N. E., Kositangool, P. & Doncic, A., Sep 6 2018, In : Molecular Cell. 71, 5, p. 733-744.e11

Research output: Contribution to journalArticle

Saccharomycetales
Meiosis
Color
Bayes Theorem
Uncertainty
1 Citation (Scopus)

Putting Evolution to Work

Ranganathan, R., Nov 29 2018, In : Cell. 175, 6, p. 1449-1451 3 p.

Research output: Contribution to journalShort survey

Nobel Prize
Protein Engineering
France
Proteins
2017
8 Citations (Scopus)

A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins

Xiao, L., Diao, J., Greene, DA., Wang, J. & Luo, R., Jul 11 2017, In : Journal of Chemical Theory and Computation. 13, 7, p. 3398-3412 15 p.

Research output: Contribution to journalArticle

Ion Channels
membranes
continuums
proteins
Proteins
5 Citations (Scopus)

An evolution-based strategy for engineering allosteric regulation

Pincus, D., Resnekov, O. & Reynolds, K. A., Apr 28 2017, In : Physical Biology. 14, 2, 025002.

Research output: Contribution to journalArticle

Allosteric Regulation
Artificial Cells
Biosensing Techniques
Membrane Proteins
Proteins
8 Citations (Scopus)

Conserved amino acid networks modulate discrete functional properties in an enzyme superfamily

Narayanan, C., Gagné, D., Reynolds, K. A. & Doucet, N., Dec 1 2017, In : Scientific Reports. 7, 1, 3207.

Research output: Contribution to journalArticle

Pancreatic Ribonuclease
Amino Acids
Enzymes
Ribonucleases
15 Citations (Scopus)

Deconstruction of the ras switching cycle through saturation mutagenesis

Bandaru, P., Shah, N. H., Bhattacharyya, M., Barton, J. P., Kondo, Y., Cofsky, J. C., Gee, C. L., Chakraborty, A. K., Kortemme, T., Ranganathan, R. & Kuriyan, J., Jul 7 2017, In : eLife. 6, e27810.

Research output: Contribution to journalArticle

Mutagenesis
Conservation
Nucleotides
GTPase-Activating Proteins
ras Proteins
9 Citations (Scopus)

Fighting against evolution of antibiotic resistance by utilizing evolvable antimicrobial drugs

Cansizoglu, M. F. & Toprak, E., May 11 2017, (Accepted/In press) In : Current Genetics. p. 1-4 4 p.

Research output: Contribution to journalArticle

Microbial Drug Resistance
Anti-Infective Agents
Pharmaceutical Preparations
Bacteria
Bacterial Genes
5 Citations (Scopus)

Increased substrate affinity in the Escherichia coli L28R dihydrofolate reductase mutant causes trimethoprim resistance

Abdizadeh, H., Tamer, Y. T., Acar, O., Toprak, E., Atilgan, A. R. & Atilgan, C., 2017, In : Physical Chemistry Chemical Physics. 19, 18, p. 11416-11428 13 p.

Research output: Contribution to journalArticle

Tetrahydrofolate Dehydrogenase
Trimethoprim
Escherichia
Escherichia coli
affinity
1 Citation (Scopus)

Leveraging symmetry to predict self-assembly of multiple polymers

Lin, M. M., Sep 1 2017, In : Chemical Physics Letters. 683, p. 347-351 5 p.

Research output: Contribution to journalArticle

Self assembly
Conformations
self assembly
Polymers
proteins
21 Citations (Scopus)

Measurement of cortical elasticity in Drosophila melanogaster embryos using ferrofluids

Doubrovinski, K., Swan, M., Polyakov, O. & Wieschaus, E. F., Jan 31 2017, In : Proceedings of the National Academy of Sciences of the United States of America. 114, 5, p. 1051-1056 6 p.

Research output: Contribution to journalArticle

Elasticity
Drosophila melanogaster
Morphogenesis
Embryonic Structures
Cytoplasm
1 Citation (Scopus)

On the Race to Starvation: How Do Bacteria Survive High Doses of Antibiotics?

Tamer, Y. T. & Toprak, E., Jan 1 2017, In : Molecular Cell. 68, 6, p. 1134-1146.e6

Research output: Contribution to journalShort survey

Starvation
Anti-Bacterial Agents
Bacteria
Food
Growth
2016
26 Citations (Scopus)

An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor

Shah, N. H., Wang, Q., Yan, Q., Karandur, D., Kadlecek, T. A., Fallahee, I. R., Russ, W. P., Ranganathan, R., Weiss, A. & Kuriyan, J., Oct 4 2016, In : eLife. 5, OCTOBER2016, e20105.

Research output: Contribution to journalArticle

T-Cell Antigen Receptor
Static Electricity
Electrostatics
Phosphotransferases
T-cells
1 Citation (Scopus)

A protocol for functional assessment of whole-protein saturation mutagenesis libraries utilizing high-throughput sequencing

Stiffler, M. A., Subramanian, S. K., Salinas, V. H. & Ranganathan, R., Jul 3 2016, In : Journal of Visualized Experiments. 2016, 113, e54119.

Research output: Contribution to journalArticle

Functional assessment
Mutagenesis
Libraries
Amino acids
Throughput
96 Citations (Scopus)

Crystal structure of the human sterol transporter ABCG5/ABCG8

Lee, J. Y., Kinch, L. N., Borek, D. M., Wang, J., Wang, J., Urbatsch, I. L., Xie, X. S., Grishin, N. V., Cohen, J. C., Otwinowski, Z., Hobbs, H. H. & Rosenbaum, D. M., May 4 2016, In : Nature. 533, 7604, p. 561-564 4 p.

Research output: Contribution to journalArticle

Sterols
ATP-Binding Cassette Transporters
Nucleotides
Mutation
Lipid Bilayers
6 Citations (Scopus)

Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore

Wray, R., Iscla, I., Gao, Y., Li, H., Wang, J. & Blount, P., Jun 9 2016, In : PLoS Biology. 14, 6, e1002473.

Research output: Contribution to journalArticle

Dihydrostreptomycin Sulfate
dihydrostreptomycin
osmolarity
Genetic Testing
Protein Biosynthesis
42 Citations (Scopus)

Electric-field-stimulated protein mechanics

Hekstra, D. R., White, K. I., Socolich, M. A., Henning, R. W., Šrajer, V. & Ranganathan, R., Dec 15 2016, In : Nature. 540, 7633, p. 400-405 6 p.

Research output: Contribution to journalArticle

Mechanics
PDZ Domains
Proteins
X Ray Crystallography
Ligands

Erratum: Mechanical slowing-down of cytoplasmic diffusion allows in vivo counting of proteins in individual cells (Nature Communications (2016) 7 (11641) DOI: 10.1038/ncomms11641)

Okumus, B., Landgraf, D., Lai, G. C., Bakshi, S., Arias-Castro, J. C., Yildiz, S., Huh, D., Fernandez-Lopez, R., Peterson, C. N., Toprak, E., El Karoui, M. & Paulsson, J., Jun 24 2016, In : Nature Communications. 7, 12130.

Research output: Contribution to journalComment/debate

Communication
Proteins
24 Citations (Scopus)

Evolution-Based Functional Decomposition of Proteins

Rivoire, O., Reynolds, K. A. & Ranganathan, R., Jun 1 2016, In : PLoS Computational Biology. 12, 6, e1004817.

Research output: Contribution to journalArticle

protein degradation
Sector
decomposition
Amino Acids
Amino acids
120 Citations (Scopus)

High-resolution crystal structure of the human CB1 cannabinoid receptor

Shao, Z., Yin, J., Chapman, K., Grzemska, M., Clark, L., Wang, J. & Rosenbaum, D. M., Dec 22 2016, In : Nature. 540, 7634, p. 602-606 5 p.

Research output: Contribution to journalArticle

Cannabinoid Receptor CB1
G-Protein-Coupled Receptors
Cannabinoid Receptors
Endocannabinoids
Dronabinol
2 Citations (Scopus)

In Silico Chemogenomics Knowledgebase and Computational System Neuropharmacology Approach for Cannabinoid Drug Research

Xie, X. Q., Wang, L., Wang, J., Xie, Z., Yang, P. & Ouyang, Q., May 13 2016, General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Elsevier Inc., Vol. 3. p. 183-195 13 p.

Research output: Chapter in Book/Report/Conference proceedingChapter

Neuropharmacology
Knowledge Bases
Cannabinoids
Polypharmacology
Computer Simulation
18 Citations (Scopus)

Mechanical slowing-down of cytoplasmic diffusion allows in vivo counting of proteins in individual cells

Okumus, B., Landgraf, D., Lai, G. C., Bakhsi, S., Arias-Castro, J. C., Yildiz, S., Huh, D., Fernandez-Lopez, R., Peterson, C. N., Toprak, E., El Karoui, M. & Paulsson, J., May 18 2016, In : Nature Communications. 7, 11641.

Research output: Contribution to journalArticle

counting
proteins
Escherichia
cells
Escherichia coli
35 Citations (Scopus)

Origins of Allostery and Evolvability in Proteins: A Case Study

Raman, A. S., White, K. I. & Ranganathan, R., Jul 14 2016, In : Cell. 166, 2, p. 468-481 14 p.

Research output: Contribution to journalArticle

Staphylococcal Protein A
Mutation
Ligands
Catalytic Domain
Proteins
21 Citations (Scopus)

Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

Ayhan, D. H., Tamer, Y. T., Akbar, M., Bailey, S. M., Wong, M., Daly, S. M., Greenberg, D. E. & Toprak, E., Sep 15 2016, In : PLoS Biology. 14, 9, e1002552.

Research output: Contribution to journalArticle

Bacterial Genes
Genes
antibiotics
Anti-Bacterial Agents
Oligomers
7 Citations (Scopus)

Switch-like Transitions Insulate Network Motifs to Modularize Biological Networks

Atay, O., Doncic, A. & Skotheim, J. M., Aug 24 2016, In : Cell Systems. 3, 2, p. 121-132 12 p.

Research output: Contribution to journalArticle

Cell Cycle
Pheromones
Saccharomyces cerevisiae
22 Citations (Scopus)

The Context-Dependence of Mutations: A Linkage of Formalisms

Poelwijk, F. J., Krishna, V. & Ranganathan, R., Jun 1 2016, In : PLoS Computational Biology. 12, 6, e1004771.

Research output: Contribution to journalArticle

6 Citations (Scopus)

Timing Correlations in Proteins Predict Functional Modules and Dynamic Allostery

Lin, M. M., May 4 2016, In : Journal of the American Chemical Society. 138, 15, p. 5036-5043 8 p.

Research output: Contribution to journalArticle

Proteins
Dihedral angle
Communication
2015
16 Citations (Scopus)

Advances in computationally modeling human oral bioavailability

Wang, J. & Hou, T., Jun 23 2015, In : Advanced Drug Delivery Reviews. 86, p. 11-16 6 p.

Research output: Contribution to journalArticle

Biological Availability
Quantitative Structure-Activity Relationship
Drug Discovery
Computer Simulation
Pharmacokinetics
Methyltransferases
Post Translational Protein Processing
Lysine
Enzymes
Proteins
16 Citations (Scopus)

Compartmentalization of a bistable switch enables memory to cross a feedback-driven transition

Doncic, A., Atay, O., Valk, E., Grande, A., Bush, A., Vasen, G., Colman-Lerner, A., Loog, M. & Skotheim, J. M., Mar 15 2015, In : Cell. 160, 6, p. 1182-1195 14 p.

Research output: Contribution to journalArticle

Switches
Feedback
Data storage equipment
Pheromones
Eukaryotic Cells
2 Citations (Scopus)

Cooperativity leads to temporally-correlated fluctuations in the bacteriophage lambda genetic switch

Shenker, J. Q. & Lin, M. M., Apr 8 2015, In : Frontiers in Plant Science. 6, APR, 214.

Research output: Contribution to journalArticle

bacteriophages
cooperatives
lysogeny
binding sites
DNA
53 Citations (Scopus)

Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes

Palmer, A. C., Toprak, E., Baym, M., Kim, S., Veres, A., Bershtein, S. & Kishony, R., Jun 10 2015, In : Nature Communications. 6, 7385.

Research output: Contribution to journalArticle

Tetrahydrofolate Dehydrogenase
Trimethoprim
fitness
antibiotics
Microbial Drug Resistance
73 Citations (Scopus)

Evolvability as a Function of Purifying Selection in TEM-1 β-Lactamase

Stiffler, M. A., Hekstra, D. R. & Ranganathan, R., Feb 26 2015, In : Cell. 160, 5, p. 882-892 11 p.

Research output: Contribution to journalArticle

Ampicillin
Cefotaxime
Transmission electron microscopy
Mutation
Ampicillin Resistance
23 Citations (Scopus)

Quantifying the Determinants of Evolutionary Dynamics Leading to Drug Resistance

Chevereau, G., Dravecká, M., Batur, T., Guvenek, A., Ayhan, D. H., Toprak, E. & Bollenbach, T., Nov 18 2015, In : PLoS Biology. 13, 11, e1002299.

Research output: Contribution to journalArticle

drug resistance
Drug Resistance
drugs
Pharmaceutical Preparations
Nitrofurantoin
89 Citations (Scopus)

The application of in silico drug-likeness predictions in pharmaceutical research

Tian, S., Wang, J., Li, Y., Li, D., Xu, L. & Hou, T., Jun 23 2015, In : Advanced Drug Delivery Reviews. 86, p. 2-10 9 p.

Research output: Contribution to journalArticle

Computer Simulation
Pharmaceutical Preparations
Drug Evaluation
Chinese Traditional Medicine
Molecular Structure