Publications

(* indicates co-corresponding authors)

bioRxiv preprints

(we post a subset of our papers to bioRxiv at the time that they are submitted to a journal)

Negative feedback of cyclic di-GMP levels optimizes switching between sessile and motile lifestyles in Vibrio cholerae. Aathmaja Anandhi Rangarajan,  Jeremy W. Schroeder, Rebecca L. Hurto,  Geoffrey B. Severin,  Macy E. Pell,  Meng-Lun Hsieh,  Christopher M. Waters*,  and Lydia Freddolino*. [html]

Multiscale regulation of nutrient stress responses in Escherichia coli from chromatin structure to small regulatory RNAs. Alyssa M. Ekdahl, Tatiana Julien, Sahana Suraj, Judith Kribelbauer, Saeed Tavazoie, Lydia Freddolino*, and Lydia M. Contreras*. [html]

StarFunc: fusing template-based and deep learning approaches for accurate protein function prediction. Chengxin Zhang*, Quancheng Liu, and Lydia Freddolino*. [html]

ShapeME: A tool and web front-end for de novo discovery of structural motifs underpinning protein-DNA interactions. Jeremy W. Schroeder*, Michael B. Wolfe, and Lydia Freddolino*. [html]

DNA methylation affects gene expression but not global chromatin structure in Escherichia coli. Willow J. Morgan, Haley M. Amemiya, and Lydia Freddolino. [html]

2025

Viperin expression leads to downregulation of mitochondrial genes through misincorporation of ddhCTP by mitochondrial RNA polymerase. Srijoni Majhi, Pronay Roy, Minshik Jo, Jiying Liu, Rebecca Hurto, Lydia Freddolino, and E. Neil G. Marsh. Journal of Biological Chemistry, in press, 2025. [html ]

Polyphosphate: The “Dark Matter” of Bacterial Chromatin Structure. Lisa R. Racki* and Lydia Freddolino*. Molecular Microbiology, 123(3):279-293, 2025. [html]  

Future directions of the prokaryotic chromosome field. E.A. Abbondanzieri et al., Molecular Microbiology, 123(2):89-100, 2025. [html]

2024

InterLabelGO+: Unraveling label correlations in protein function prediction. Quancheng Liu, Chengxin Zhang*, and Lydia Freddolino*. Bioinformatics, btae655, 2024. [html]

A large-scale assessment of sequence database search tools for homology-based protein function prediction. Chengxin Zhang* and Lydia Freddolino*. Briefings in Bioinformatics, 25:bbae349, 2024. [html]

Tracking live-cell single-molecule dynamics enables measurements of heterochromatin-associated protein–protein interactions. Ziyuan Chen, Melissa Seman, Ali Farhat, Yekaterina Fyodorova, Saikat Biswas, Alexander Levashkevich, Lydia Freddolino*, Julie Suzanne Biteen*, and Kaushik Ragunathan*. Nucleic Acids Research, gkae692, 2024. [html]

FURNA: a database for function annotations of RNA structures. Chengxin Zhang* and Lydia Freddolino*. PLoS Biology, 22(7):e3002476, 2024. [html]

High-Throughput Mapping of Chromosomal Conformations in E. coli Under Physiological Conditions Using Massively Multiplexed Mu Transposition. Khang Ho, Sonya K. Royzenblat, Brady Wilkins, Rasika Harshey, and Lydia Freddolino. Methods in Molecular Biology, in press.

Nucleoid-associated proteins shape the global protein occupancy and transcriptional landscape of a clinical isolate of Vibrio cholerae. Yulduz Rakibova, Drew T. Dunham, Kimberly D. Seed, and Lydia Freddolino. mSphere, 9(7):e00011-24, 2024. [html]

Spatio-temporal organization of the E. coli chromosome from base to cellular length scales. Sonya K. Royzenblat and Lydia Freddolino. EcoSal Plus, eesp-0001-2022, 2024.

Enricherator: A Bayesian Method for Inferring Regularized Genome-wide Enrichments from Sequencing Count Data. Jeremy W. Schroeder and Lydia Freddolino. J. Molecular Biology, 436(17):168567, 2024. [html]

Regulation of the Drosophila transcriptome by Pumilio and the CCR4-NOT deadenylase complex. Rebecca J. Haugen, Catherine Barnier, Nathan D. Elrod, Hua Luo, Madeline K. Jensen, Ping Ji, Craig A. Smibert, Howard D. Lipshitz, Eric J. Wagner, Lydia Freddolino, and Aaron C Goldstrohm. RNA 079813.123, 2024. [html]

DEMO-EM2: assembling protein complex structures from cryo-EM maps through intertwined chain and domain fitting. Ziying Zhang, Yaxian Cai, Biao Zhang, Wei Zheng, Lydia Freddolino*, Guijun Zhang*, and Xiaogen Zhou*. Briefings in Bioinformatics 25:bbae113, 2024. [doi]

Improving deep learning protein monomer and complex structure prediction using DeepMSA2 with huge metagenomics data.  Wei Zheng,  Qiqige Wuyun, Yang Li, Chengxin Zhang, Lydia Freddolino*, and Yang Zhang. Nature Methods, 21:279-289, 2024. [html ]

2023

Deep mutational scanning highlights a new role for cytosolic regions in Hrd1 function. Brian G. Peterson, Jiwon Hwang, Jennifer E. Russ, Jeremy Schroeder, Lydia Freddolino, and Ryan D. Baldridge. Cell Reports, 42:113451, 2023. [doi]

Integrating end-to-end learning with deep geometrical potentials for ab initio RNA structure prediction. Yang Li, Chengxin Zhang, Chenjie Feng, Lydia Freddolino*, and Yang Zhang*. Nature Communications, 14:5745, 2023. [doi]

Integrating deep learning, threading alignments, and multi-MSA strategy for high-quality protein monomer and complex structure prediction in CASP15. Wei Zheng, Qiqige Wuyun, Lydia Freddolino, and Yang Zhang. Proteins: Structure, Function, and Bioinformatics, 91:1684-1703, 2023. [pdf ]

BioLiP2: an updated structure database for biologically relevant ligand–protein interactions. Chengxin Zhang, Xi Zhang, Lydia Freddolino*, and Yang Zhang*. Nucleic Acids Research, gkad630, 2023. [html]

VMD as a Platform for Interactive Small Molecule Preparation and Visualization in Quantum and Classical Simulations. Mariano Spivak, John E. Stone, Joao Ribeiro, Jan Saam, Lydia Freddolino, Rafael Bernardi, and Emad Tajkhorshid. J. Chem. Inform. Modeling, in press.

Protein target highlights in CASP15: Analysis of models by structure providers. Leila T. Alexander et al. Proteins: Structure, Function, and Bioinformatics, in press.

RNase H genes cause distinct impacts on RNA:DNA hybrid formation and mutagenesis genome-wide. Jeremy W. Schroeder, Rebecca L. Hurto, Justin R. Randall, Katherine J. Wozniak, Taylor A. Timko, Taylor M. Nye, Jue D. Wang, Lydia Freddolino*, and Lyle A. Simmons*. Science Advances, 9:eadi5945, 2023. [html]

E. coli Leucine-responsive regulatory protein bridges DNA in vivo and tunably dissociates in the presence of exogenous leucine. Christine A. Ziegler and Lydia Freddolino. mBio e02690-22, 2023. [html]

Nutrigenomic regulation of sensory plasticity.  Hayeon Sung, Anoumid Vaziri, Daniel Wilinski, Riley KR Woerner, Lydia Freddolino, and Monica Dus eLife 12:e83979, 2023.[html]

2022

TripletGO: Integrating Transcript Expression Profiles with Protein Homology Inferences for Gene Function Prediction. Yi-Heng Zhu, Chengxin Zhang, Yan Liu, Gilbert S. Omenn, Lydia Freddolino, Dong-Jun Yu, and Yang Zhang. Genomics, Proteomics, & Bioinformatics, 20(5):1013-1027, 2022. [html]

Genetic context effects can override canonical cis regulatory elements in Escherichia coli. Scott A. Scholz*, Chase D. Lindeboom, and Lydia Freddolino*. Nucleic Acids Res. gkac787, 2022. [html ]

Escherichia coli YigI is a conserved γ-proteobacterial acyl-CoA thioesterase permitting metabolism of unusual fatty acid substrates. Michael Schmidt, Theresa Proctor, Rucheng Diao, and Lydia Freddolino.  J. Bacteriol. 24(8):e00014-22, 2022. [html]

Mapping biochemical states associated with HP1 target recognition at sites of heterochromatin formation in living cells. Saikat Biswas, Josh Karslake, Ziyuan Chen, Ali Farhat, Lydia Freddolino*, Julie Suzanne Biteen*, and Kaushik Ragunathan*. Science Advances, 8(27):abk0793, 2022. [html]

Integrating Transcript Expression Profiles with Protein Homology Inferences for High-Accuracy Gene Function Annotations. Yi-Heng Zhu, Chengxin Zhang, Yan Liu, Gilbert S. Omenn, Lydia Freddolino, Dong-Jun Yu, and Yang Zhang. Genomics, Proteomics, & Bioinformatics, in press. [html]

PEPPI: Whole-proteome protein-protein interaction prediction through structure and sequence similarity, functional association, and machine learning.  Eric W. Bell, Jacob H. Schwartz, Lydia Freddolino*,  and Yang Zhang*. J. Mol. Biol. 434(11):167530, 2022. [html]

LOMETS3: integrating deep learning and profile alignment for advanced protein template recognition and function annotation.  Wei Zheng, Qiqige Wuyun, Xiaogen Zhou, Yang Li, Lydia Freddolino*, and Yang Zhang*. Nucleic Acids Res. gkac248, 2022. [html]

Epistasis at the SARS-CoV-2 RBD Interface and the Propitiously Boring Implications for Vaccine Escape. Nash D. Rochman, Guilhem Faure, Yuri I. Wolf, Lydia Freddolino, Feng Zhang, and Eugene V. Koonin. mBio 13(2):e00135-22, 2022. [html]

CR-I-TASSER: assemble protein structures from cryo-EM density maps using deep convolutional neural networks. Xi Zhang, Biao Zhang, Lydia Freddolino*, and Yang Zhang*. Nature Methods 19:195-204, 2022. [html]

2021

Distinct heterochromatin-like domains promote transcriptional memory and silence parasitic genetic elements in bacteria. Haley M. Amemiya, Thomas J. Goss, Taylor M. Nye, Rebecca Hurto, Lyle A. Simmons, and Lydia Freddolino. EMBO Journal e108708, 2021. [html]

Polyphosphate drives bacterial heterochromatin formation. Francois Beaufay, Haley M. Amemiya, Jian Guan, Joseph Basalla, Ben A. Meinen, Ziyuan Chen, Rishav Mitra, James C. A. Bardwell, Julie S. Biteen,  Anthony G. Vecchiarelli, Lydia Freddolino*, and Ursula Jakob*. Science Advances 7:abk0233, 2021. [html]

Nucleoid-associated proteins shape chromatin structure and transcriptional regulation across the bacterial kingdom. Haley M. Amemiya, Jeremy Schroeder, and Lydia Freddolino. Transcription 12(4):182-218, 2021. [html]

The hepatic compensatory response to elevated systemic sulfide promotes diabetes. Roderick D. Carter et al. Cell Reports 37(6):109958, 2021. [html]

Uncovering transcriptional regulators and targets of sRNAs using an integrative data-mining approach: H-NS-regulated RseX as a Case Study. Mia Mihailovic, Alyssa Ekdahl, Angela Chen, Abigail Leistra, Bridget Li, Javier González Martínez, Matthew Law, Cindy Ejindu, Éric Massé, Lydia Freddolino, and Lydia Contreras. Front. Cell. Infec. Microbiol. 11:696533, 2021. [html]

Dynamic landscape of protein occupancy across the Escherichia coli chromosome. Lydia Freddolino*, Haley M. Amemiya, Thomas J. Goss, and Saeed Tavazoie*. PLoS Biology 19(6): e3001306, 2021. [html]

The Leucine-responsive Regulatory Proteins/Feast-Famine Regulatory Proteins: an ancient and complex class of transcriptional regulators in bacteria and archaea. Christine A. Ziegler and Lydia Freddolino. Critical Reviews in Biochemistry 56(4):373-400, 2021. [html ]

TNFRSF13B polymorphisms counteract microbial adaptation to natural IgA. Jeffrey L Platt, Mayara Garcia de Mattos Barbosa, Daniel Huynh, Adam R Lefferts, Juhi Katta, Cyra Kharas, Lydia Freddolino, Christine Marie Bassis, Christiane E Wobus, Raif Geha, Richard J Bram, Gabriel Nunez, Nobuhiko Kamada, and Marilia Cascalho. JCI Insight 6(18):e148208, 2021. [pdf ]

Functions of Essential Genes and a Scale-Free Protein Interaction Network Revealed by Structure-Based Function and Interaction Prediction for a Minimal Genome. Chengxin Zhang, Wei Zheng, Micah Cheng, Gilbert S. Omenn, Lydia Freddolino*, and Yang Zhang*. J. Proteome Research 20(2):1178-1189, 2021. [html]

2020

Persistent epigenetic reprogramming of sweet taste by diet. Anoumid Vaziri, Morteza Khabiri, Brendan T. Genaw, Christina E. May, Lydia Freddolino, and Monica Dus. Science Advances 6:eabc8492, 2020. [html]

Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide dinucleotide metabolites. Elizabeth T. Abshire, Kelsey Hughes, Rucheng Diao, Sarah Pearce, Shreekara Gopalakrishna, Raymond C. Trievel, Joanna Rorbach, Lydia Freddolino,  and Aaron C. Goldstrohm. J. Biol. Chem. 295:15112-15133, 2020. [html]

Principles of mRNA control by human PUM proteins elucidated from multi-modal experiments and integrative data analysis. Michael B. Wolfe, Trista L. Schagat, Michelle T. Paulsen,  Brian Magnuson, Mats Ljungman, Daeyoon Park, Chi Zhang,  Zachary T Campbell,  Aaron C Goldstrohm*,  and Lydia Freddolino*. RNA 26:1680-1703, 2020. [html]

A Thermosensitive Phase-variable Epigenetic Switch: pap Revisited. Mario Zamora, Christine A. Ziegler, Lydia Freddolino, and Alan J. Wolfe. Microbiology and Molecular Biology Reviews 84:e00030-17, 2020.  [html]

Detecting Gene Ontology misannotations using taxon-specific rate ratio comparisons. Xiaoqiong Wei, Chengxin Zhang, Lydia Freddolino*, and Yang Zhang*. Bioinformatics btaa548, 2020. [html]

A Well-Mixed E. coli Genome: Widespread Contacts Revealed by Tracking Mu Transposition. David M. Walker, Lydia Freddolino*, and Rasika Harshey*. Cell 180:701-716, 2020. [html]

2019

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens. The CAFA3 consortium (Naihui Zhou et al.). Genome Biology 20:1-23, 2019. [html]

Unique repression domains of Pumilio utilize deadenylation and decapping factors to accelerate destruction of target mRNAs. René M Arvola, Chung-Te Chang, Joseph P Buytendorp, Yevgen Levdansky, Eugene Valkov, Lydia Freddolino, and Aaron C Goldstrohm. Nucleic Acids Res. gk71187, 2019. [html]

Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster. Daniel Wilinski, Jasmine Winzeler, William Duren, Jenna L. Persons, Kristina J. Holme, Johan Mosquera, Morteza Khabiri, Jason M. Kinchen, Lydia Freddolino, Alla Karnovsky and Monica Dus. Nature Comm. 10:4052, 2019. [html]

High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster. Christina E. May, Anoumid Vaziri, Yong Qi Lin, Olga Grushko, Morteza Khabiri, Qiao-Ping Wang, Kristina J. Holme, Scott D. Pletcher, Lydia Freddolino, G. Gregory Neely, and Monica Dus. Cell Reports, 27:1675-1685, 2019. [html]

Introducing a Spectrum of Long-Range Genomic Deletions in Human Embryonic Stem Cells Using Type I CRISPR-Cas. Adam E. Dolan, Zhonggang Hou, Yibei Xiao, Max J. Gramelspacher, Jaewon Heo, Sara E. Howden, Lydia Freddolino, Ailong Ke, and Yan Zhang. Molecular Cell, 74:936-950, 2019. [html]

Applications of molecular modeling to flavoproteins: Insights and challenges. Emil Sjulstok, Ilia A. Solov'yov, and Lydia Freddolino. Methods in Enzymology, 620:277-314, 2019. [html]

High-Resolution Mapping of the Escherichia coli Chromosome Reveals Positions of High and Low Transcription. Scott A. Scholz, Rucheng Diao, Michael B. Wolfe, Elayne M. Fivenson, Xiaoxia Nina Lin*, and Lydia Freddolino*. Cell Systems 8:212-225, 2019. [html]

Global analysis of RNA metabolism using bio-orthogonal labeling coupled with next-generation RNA sequencing. Michael B. Wolfe, Aaron C. Goldstrohm*, and Lydia Freddolino*. Methods, 155:88-103, 2019. [html]

Escherichia coli Lrp regulates one-third of the genome via direct, cooperative, and indirect routes. Grace M. Kroner, Michael B. Wolfe, and Lydia Freddolino. Journal of Bacteriology, 201:e00411-18, 2019. [html]

2018

The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells. Elizabeth Abshire, Jennifer Chasseur, Jennifer Bohn, Paul Del Rizzo, Lydia Freddolino, Aaron Goldstrohm, and Raymond Trievel. Nucleic Acids Research, 46(12):6257-6270, 2018. [html]

Cellular Adaptation Through Fitness-Directed Transcriptional Tuning. Lydia Freddolino, Jamie Yang, Amir Roknabadi, and Saeed Tavazoie. eLife, 7:e31867, 2018.  [html]

MetaGO: Predicting Gene Ontology of non-homologous proteins through low-resolution protein structure prediction and protein-protein network mapping. Chengxin Zhang, Wei Zheng, Lydia Freddolino, and Yang Zhang. Journal of Molecular Biology, 430(15):2256-2265, 2018. [html]

Identification of diverse target RNAs that are functionally regulated by human Pumilio proteins. Jennifer A. Bohn, Jamie L. Van Etten, Trista L. Schagat, Brittany M. Bowman, Richard C. McEachin, Lydia Freddolino*, and Aaron C. Goldstrohm*. Nucleic Acids Research, 46:362-386, 2018. [html]

2015-2017

Structure of FlgK reveals the divergence of the bacterial Hook-Filament Junction of Campylobacter. Paula V. Bulieris, Nausad H. Shaikh, Lydia Freddolino, and Fadel A. Samatey. Scientific Reports, 7:15743, 2017. [html]

An intrinsically disordered linker controlling the formation and the stability of the bacterial flagellar hook. Clive Barker, Irina Meshcheryakova, Alla Kostyukova, Lydia Freddolino, and Fadel Samatey. BMC Biology, 15:97, 2017. [html]

COFACTOR: Improved protein function prediction by combining structure, sequence, and protein-protein interaction information. Chengxin Zhang, Lydia Freddolino*, and Yang Zhang*. Nucleic Acids Research, W1:W291-W299, 2017. [html]

Deficiencies in molecular dynamics simulation-based prediction of protein-DNA binding free energy landscapes. Morteza Khabiri and Lydia Freddolino. Journal of Physical Chemistry B, 121:5151-5161, 2017. [html]

QwikMD—Integrative Molecular Dynamics Toolkit for Novices and Experts. João V Ribeiro, Rafael C Bernardi, Till Rudack, John E Stone, James C Phillips, Lydia Freddolino, and Klaus Schulten. Scientific Reports, 6: 26536, 2016. [html]

Interfacial activation of Candida antarctica lipase B: combined evidence from experiment and simulation. Themistoklis Zisis, Lydia Freddolino, Petri Turunen, Muriel CF van Teeseling, Alan E Rowan, and Kerstin G Blank. Biochemistry, 54:5969-5979, 2015. [html]

Representative examples of older work

Revealing the genetic basis of natural bacterial phenotypic divergence. Lydia Freddolino, Hani Goodarzi, and Saeed Tavazoie. Journal of Bacteriology, 196:825-839, 2014. [html]

Bacterial Adaptation through Loss of Function. Alison K. Hottes, Lydia Freddolino, Anupama Khare, Zachary N. Donnell, Julia C. Liu, and Saeed Tavazoie. PLoS Genetics, 9(7): e1003617, 2013. [html]

The Dawn of Virtual Cell Biology. Lydia Freddolino and Saeed Tavazoie. Cell, 150:248-250, 2012. [html]

Beyond Homeostasis: A Predictive-Dynamic Framework for Understanding Cellular Behavior. Lydia Freddolino and Saeed Tavazoie. Annual Review of Cell and Developmental Biology, 28:363-384, 2012. [html]

Fitness Landscape Transformation through a Single Amino Acid Change in the Rho Terminator. Lydia Freddolino, Hani Goodarzi, and Saeed Tavazoie. PLoS Genetics, 8(5):e1002744, 2012. [html]

Challenges in protein-folding simulations. Lydia Freddolino, Christopher B Harrison, Yanxin Liu, Klaus Schulten. Nature Physics, 6:751-758, 2010. [html]

Common structural transitions in explicit-solvent simulations of villin headpiece folding. Lydia Freddolino and Klaus Schulten. Biophysical Journal, 97:2338-2347, 2009. [html]

Force field bias in protein folding simulations. Lydia Freddolino, Sanghyun Park, Benoit Roux, and Klaus Schulten. Biophysical Journal, 96:3772-3780, 2009. [html]

Molecular dynamics simulations of the complete satellite tobacco mosaic virus. Lydia Freddolino, Anton S. Arkhipov, Steven B. Larson, Alexander McPherson, and Klaus Schulten. Structure, 14:437-449, 2006. [html]