(* 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)

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 P. Lydia Freddolino. [html]

FURNA: a database for function annotations of RNA structures. Chengxin Zhang* and P. Lydia Freddolino*. [html ]

A large-scale assessment of sequence database search tools for homology-based protein function prediction. Chengxin Zhang* and P. Lydia Freddolino*. [html ]

H3K9 methylation enhances HP1-associated epigenetic silencing complex assembly and suppresses off-chromatin binding. Ziyuan Chen, Melissa Seman, Ali Farhat, Yekaterina Fyodorova, Saikat Biswas, Alexander Levashkevich, P. Lydia Freddolino, Julie Suzanne Biteen*, and Kaushik Ragunathan*. [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*. Briefinds 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, P.  Lydia Freddolino*, and Yang Zhang. Nature Methods, 21:279-289, 2024. [html ]


Deep mutational scanning highlights a new role for cytosolic regions in Hrd1 function. Brian G. Peterson, Jiwon Hwang, Jennifer E. Russ, Jeremy Schroeder, P. 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, P. 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, P. L. 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, P. L. 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, P. L. 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, P. L. Freddolino*, and Lyle A. Simmons*. Science Advances, in press. [preprint]

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

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


TripletGO: Integrating Transcript Expression Profiles with Protein Homology Inferences for Gene Function Prediction. Yi-Heng Zhu, Chengxin Zhang, Yan Liu, Gilbert S. Omenn, P. L. 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 P. L. 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 P. L. 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, P. L. 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, P. L. 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, P. L. 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, P. L. 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, P. L. 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, P. L. Freddolino*, and Yang Zhang*. Nature Methods 19:195-204, 2022. [html]


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 P. L. 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, P. L. 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 P. L. 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, P. L. Freddolino, and Lydia Contreras. Front. Cell. Infec. Microbiol. 11:696533, 2021. [html]

Dynamic landscape of protein occupancy across the Escherichia coli chromosome. P. L. 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 P. L. 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, P. L. 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, P. L. Freddolino*, and Yang Zhang*. J. Proteome Research 20(2):1178-1189, 2021. [html]


Persistent epigenetic reprogramming of sweet taste by diet. Anoumid Vaziri, Morteza Khabiri, Brendan T. Genaw, Christina E. May, P. L. 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, P. L. 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 P. L Freddolino*. RNA 26:1680-1703, 2020. [html]

A Thermosensitive Phase-variable Epigenetic Switch: pap Revisited. Mario Zamora, Christine A. Ziegler, P. L. 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, P. L. Freddolino*, and Yang Zhang*. Bioinformatics btaa548, 2020. [html]

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


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, P. L 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, P. L. 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, P. L. 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, P. L. 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 P. L. 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 P. L. 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 P. L. 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 P. L. Freddolino. Journal of Bacteriology, 201:e00411-18, 2019. [html]


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, P. L. Freddolino, Aaron Goldstrohm, and Raymond Trievel. Nucleic Acids Research, 46(12):6257-6270, 2018. [html]

Cellular Adaptation Through Fitness-Directed Transcriptional Tuning. P. L. 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, P. L. 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, P. L. Freddolino*, and Aaron C. Goldstrohm*. Nucleic Acids Research, 46:362-386, 2018. [html]


Structure of FlgK reveals the divergence of the bacterial Hook-Filament Junction of Campylobacter. Paula V. Bulieris, Nausad H. Shaikh, P. L. 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, P. L. 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, P. L. 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 P. L. 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, P. L. 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, P. L 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. P. L. Freddolino, Hani Goodarzi, and Saeed Tavazoie. Journal of Bacteriology, 196:825-839, 2014. [html]

Bacterial Adaptation through Loss of Function. Alison K. Hottes, P. L. 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. P. L. Freddolino and Saeed Tavazoie. Cell, 150:248-250, 2012. [html]

Beyond Homeostasis: A Predictive-Dynamic Framework for Understanding Cellular Behavior. P. L. 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. P. L. Freddolino, Hani Goodarzi, and Saeed Tavazoie. PLoS Genetics, 8(5):e1002744, 2012. [html]

Challenges in protein-folding simulations. P. L. 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. P. L. Freddolino and Klaus Schulten. Biophysical Journal, 97:2338-2347, 2009. [html]

Force field bias in protein folding simulations. P. L. 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. P. L. Freddolino, Anton S. Arkhipov, Steven B. Larson, Alexander McPherson, and Klaus Schulten. Structure, 14:437-449, 2006. [html]