Fast and accurate protein structure search with Foldseek

Basic local alignment search tool

Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works

Highly accurate protein structure prediction with AlphaFold

Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works

AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models

Varadi, M., Anyango, S., Deshpande, M., Nair, S., Natassia, C., Yordanova, G., Yuan, D., Stroe, O., Wood, G., Laydon, A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1061 · Cited by 7,850 · see citing works

Accelerated Profile HMM Searches

Eddy, S. R. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002195 · Cited by 6,975 · see citing works

Accurate prediction of protein structures and interactions using a 3-track network

Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2021) · doi:10.1101/2021.06.14.448402 · Cited by 5,542 · see citing works

Evolutionary-scale prediction of atomic level protein structure with a language model

Lin, Z., Akin, H., Rao, R., Hie, B., Zhu, Z., Lu, W., Smetanin, N., Verkuil, R., Kabeli, O., Shmueli, Y., et al. (2022) · doi:10.1101/2022.07.20.500902 · Cited by 5,523 · see citing works

Sensitive protein alignments at tree-of-life scale using DIAMOND

Buchfink, B., Reuter, K., & Drost, H.-G. (2021) · Nature Methods · doi:10.1038/s41592-021-01101-x · Cited by 5,097 · see citing works

MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets

Steinegger, M., & Söding, J. (2017) · Nature Biotechnology · doi:10.1038/nbt.3988 · Cited by 4,840 · see citing works

TM-align: a protein structure alignment algorithm based on the TM-score

Zhang, Y. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki524 · Cited by 3,774 · see citing works

Protein structure alignment by incremental combinatorial extension (CE) of the optimal path.

Shindyalov, I., & Bourne, P. (1998) · Protein Engineering · doi:10.1093/protein/11.9.739 · Cited by 2,199 · see citing works

Structure of the RNA-dependent RNA polymerase from COVID-19 virus

Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., Wang, T., Sun, Q., Ming, Z., Zhang, L., et al. (2020) · Science · doi:10.1126/science.abb7498 · Cited by 1,614 · see citing works

RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences

Burley, S. K., Bhikadiya, C., Bi, C., Bittrich, S., Chen, L., Crichlow, G. V., Christie, C. H., Dalenberg, K., Di Costanzo, L., Duarte, J. M., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1038 · Cited by 1,581 · see citing works

mixtools : An R Package for Analyzing Finite Mixture Models

Benaglia, T., Chauveau, D., Hunter, D. R., & Young, D. S. (2009) · Journal of Statistical Software · doi:10.18637/jss.v032.i06 · Cited by 1,351 · see citing works

RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy

Burley, S. K., Berman, H. M., Bhikadiya, C., Bi, C., Chen, L., Costanzo, L. D., Christie, C. H., Dalenberg, K., Duarte, J. M., Dutta, S., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1004 · Cited by 1,249 · see citing works

Protein Data Bank: the single global archive for 3D macromolecular structure data

wwPDB consortium, Burley, S. K., Berman, H. M., Bhikadiya, C., Bi, C., Chen, L., Costanzo, L. D., Christie, C., Duarte, J. M., Dutta, S., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky949 · Cited by 1,163 · see citing works

HH-suite3 for fast remote homology detection and deep protein annotation

Steinegger, M., Meier, M., Mirdita, M., Vöhringer, H., Haunsberger, S. J., & Söding, J. (2019) · BMC Bioinformatics · doi:10.1186/s12859-019-3019-7 · Cited by 1,145 · see citing works

lDDT: a local superposition-free score for comparing protein structures and models using distance difference tests

Mariani, V., Biasini, M., Barbato, A., & Schwede, T. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt473 · Cited by 1,138 · see citing works

MMseqs2 desktop and local web server app for fast, interactive sequence searches

Mirdita, M., Steinegger, M., & Söding, J. (2019) · Bioinformatics · doi:10.1093/bioinformatics/bty1057 · Cited by 618 · see citing works

Using Dali for Protein Structure Comparison

Holm, L. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0270-6_3 · Cited by 613 · see citing works

Structure is three to ten times more conserved than sequence—A study of structural response in protein cores

Illergård, K., Ardell, D. H., & Elofsson, A. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22458 · Cited by 559 · see citing works

HOMSTRAD: A database of protein structure alignments for homologous families

Mizuguchi, K., Deane, C. M., Blundell, T. L., & Overington, J. P. (1998) · Protein Science · doi:10.1002/pro.5560071126 · Cited by 501 · see citing works

NGL viewer: web-based molecular graphics for large complexes

Rose, A. S., Bradley, A. R., Valasatava, Y., Duarte, J. M., Prlić, A., & Rose, P. W. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty419 · Cited by 489 · see citing works

Striped Smith–Waterman speeds database searches six times over other SIMD implementations

Farrar, M. S. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl582 · Cited by 417 · see citing works

Fast procedure for reconstruction of full‐atom protein models from reduced representations

Rotkiewicz, P., & Skolnick, J. (2008) · Journal of Computational Chemistry · doi:10.1002/jcc.20906 · Cited by 395 · see citing works

Advances and pitfalls of protein structural alignment

Hasegawa, H., & Holm, L. (2009) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2009.04.003 · Cited by 369 · see citing works

MMseqs software suite for fast and deep clustering and searching of large protein sequence sets

Hauser, M., Steinegger, M., & Söding, J. (2016) · Bioinform. · doi:10.1093/bioinformatics/btw006 · Cited by 265 · see citing works

Parasail: SIMD C library for global, semi-global, and local pairwise sequence alignments

Daily, J. A. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-0930-z · Cited by 241 · see citing works

SSW Library: An SIMD Smith-Waterman C/C++ Library for Use in Genomic Applications

Zhao, M., Lee, W.-P., Garrison, E. P., & Marth, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082138 · Cited by 239 · see citing works

SPICi: a fast clustering algorithm for large biological networks

Jiang, P., & Singh, M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq078 · Cited by 239 · see citing works

SCOPe: classification of large macromolecular structures in the structural classification of proteins—extended database

Chandonia, J., Fox, N. K., & Brenner, S. E. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1134 · Cited by 167 · see citing works

Protein structure database search and evolutionary classification

Yang, J. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl395 · Cited by 115 · see citing works

AlphaFold2 reveals commonalities and novelties in protein structure space for 21 model organisms

Bordin, N., Sillitoe, I., Nallapareddy, V., Rauer, C., Lam, S. D., Waman, V. P., Sen, N., Heinzinger, M., Littmann, M., Kim, S., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04488-9 · Cited by 103 · see citing works

Protein sequence comparison and fold recognition: progress and good-practice benchmarking

Söding, J., & Remmert, M. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.03.005 · Cited by 80 · see citing works

Algorithms, Applications, and Challenges of Protein Structure Alignment

Ma, J., & Wang, S. (2014) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-800168-4.00005-6 · Cited by 59 · see citing works

Early ribbon drawings of proteins.

Richardson, J. S. (2000) · Nature Structural Biology · doi:10.1038/77912 · Cited by 52 · see citing works

CLePAPS: FAST PAIR ALIGNMENT OF PROTEIN STRUCTURES BASED ON CONFORMATIONAL LETTERS

Wang, S., & Zheng, W. (2008) · Journal of Bioinformatics and Computational Biology · doi:10.1142/s0219720008003461 · Cited by 51 · see citing works

SA-Search: a web tool for protein structure mining based on a Structural Alphabet

Guyon, F., Camproux, A., Hochez, J., & Tufféry, P. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh467 · Cited by 49 · see citing works

Geometricus represents protein structures as shape-mers derived from moment invariants

Durairaj, J., Akdel, M., de Ridder, D., & van Dijk, A. D. J. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa839 · Cited by 47 · see citing works

BioJava 5: A community driven open-source bioinformatics library

Lafita, A., Bliven, S. E., Prlić, A., Guzenko, D., Rose, P. W., Bradley, A. R., Pavan, P., Myers-Turnbull, D., Valasatava, Y., Heuer, M., et al. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006791 · Cited by 44 · see citing works

HFSP: high speed homology-driven function annotation of proteins

Mahlich, Y., Steinegger, M., Rost, B., & Bromberg, Y. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty262 · Cited by 42 · see citing works

Foldcomp: a library and format for compressing and indexing large protein structure sets

Kim, H., Mirdita, M., & Steinegger, M. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad153 · Cited by 29 · see citing works

DeepAlign, a 3D alignment method based on regionalized deep learning for Cryo-EM

Jiménez-Moreno, A., Střelák, D., Filipovič, J., Carazo, J. M., & Sorzano, C. Ó. S. (2021) · Journal of Structural Biology · doi:10.1016/j.jsb.2021.107712 · Cited by 23 · see citing works

Towards an efficient compression of 3D coordinates of macromolecular structures

Valasatava, Y., Bradley, A. R., Rose, A., Duarte, J. M., Prlić, A., & Rose, P. W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174846 · Cited by 14 · see citing works

fast_protein_cluster: parallel and optimized clustering of large-scale protein modeling data

Hung, L., & Samudrala, R. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu098 · Cited by 12 · see citing works

Structural consequences of an amino acid deletion in the B1 domain of protein G

O’Neil, K. T., Bach, A., & DeGrado, W. F. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20001115)41:3 · Cited by 11 · see citing works

A cognitive organization theory (COT) of organizational change

van den Oord, A., Elliott, K., van Witteloostuijn, A. C., Barlage, M., Polós, L., & Rogiest, S. (2017) · Journal of Organizational Change Management · doi:10.1108/jocm-08-2016-0164 · Cited by 6 · see citing works

Evolutionary-scale prediction of atomic level protein structure with a language model

Lin, Z., Akin, H., Rao, R., Hie, B., Zhu, Z., Lu, W., Smetanin, N., Verkuil, R., Kabeli, O., Shmueli, Y., et al. (2022) · doi:10.1101/2022.07.20.500902 · Cited by 5,523 · see citing works

InterPro: the protein sequence classification resource in 2025

Blum, M., Andreeva, A. E., Florentino, L. C., Chuguransky, S., Grego, T., Hobbs, E., Pinto, B. L., Orr, A., Paysan‐Lafosse, T., Ponamareva, I., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1082 · Cited by 1,180 · see citing works

Dali server: structural unification of protein families

Holm, L. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac387 · Cited by 913 · see citing works

Simulating 500 million years of evolution with a language model

Hayes, T., Rao, R., Akin, H., Sofroniew, N. J., Oktay, D., Lin, Z., Verkuil, R., Tran, V. Q., Deaton, J., Wiggert, M., et al. (2025) · Science · doi:10.1126/science.ads0018 · Cited by 937 · see citing works

ProtGPT2 is a deep unsupervised language model for protein design

Ferruz, N., Schmidt, S., & Höcker, B. (2022) · Nature Communications · doi:10.1038/s41467-022-32007-7 · Cited by 795 · see citing works

DALI shines a light on remote homologs: One hundred discoveries

Holm, L., Laiho, A., Törönen, P., & Salgado, M. G. (2022) · Protein Science · doi:10.1002/pro.4519 · Cited by 685 · see citing works

ProGen2: Exploring the boundaries of protein language models

Nijkamp, E., Ruffolo, J. A., Weinstein, E. N., Naik, N., & Madani, A. (2023) · Cell Systems · doi:10.1016/j.cels.2023.10.002 · Cited by 480 · see citing works

Learning inverse folding from millions of predicted structuresPreprint

Hsu, C., Verkuil, R., Liu, J. J., Lin, Z., Hie, B., Sercu, T., Lerer, A. K., & Rives, A. W. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.10.487779 · Cited by 434 · see citing works

Database resources of the National Center for Biotechnology Information in 2023

Sayers, E. W., Bolton, E., Brister, J. R., Canese, K., Chan, J., Comeau, D. C., Farrell, C. M., Feldgarden, M., Fine, A. M., Funk, K., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1032 · Cited by 436 · see citing works

The Pfam protein families database: embracing AI/ML

Paysan-Lafosse, T., Andreeva, A., Blum, M., Chuguransky, S., Grego, T., Pinto, B. L., Salazar, G. A., Bileschi, M. L., Llinares-López, F., Meng-Papaxanthos, L., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae997 · Cited by 382 · see citing works

Clustering predicted structures at the scale of the known protein universe

Barrio-Hernandez, I., Yeo, J., Jänes, J., Mirdita, M., Gilchrist, C. L. M., Wein, T., Varadi, M., Velankar, S., Beltrao, P., & Steinegger, M. (2023) · Nature · doi:10.1038/s41586-023-06510-w · Cited by 362 · see citing works

Scalable emulation of protein equilibrium ensembles with generative deep learning

Lewis, S., Hempel, T., Jiménez-Luna, J., Gastegger, M., Xie, Y., Foong, A. Y. K., Satorras, V. G., Abdin, O., Veeling, B. S., Zaporozhets, I., et al. (2025) · Science · doi:10.1126/science.adv9817 · Cited by 335 · see citing works

Empowering biomedical discovery with AI agents

Gao, S., Fang, A., Huang, Y., Giunchiglia, V., Noori, A., Schwarz, J. R., Ektefaie, Y., Kondic, J., & Zitnik, M. (2024) · Cell · doi:10.1016/j.cell.2024.09.022 · Cited by 315 · see citing works

Bilingual language model for protein sequence and structure

Heinzinger, M., Weissenow, K., Sanchez, J. G., Henkel, A., Mirdita, M., Steinegger, M., & Rost, B. (2024) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqae150 · Cited by 311 · see citing works

AlphaFold Protein Structure Database and 3D-Beacons: New Data and Capabilities

Fleming, J., Magaña, P., Nair, S. S., Tsenkov, M. I., Bertoni, D., Pidruchna, I., Afonso, M. Q. L., Midlik, A., Paramval, U., Žídek, A., et al. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.168967 · Cited by 311 · see citing works

One-shot design of functional protein binders with BindCraft

Pačesa, M., Nickel, L., Schellhaas, C., Schmidt, J. H., Pyatova, E., Kissling, L., Barendse, P., Choudhury, J., Kapoor, S., Alcaraz‐Serna, A., et al. (2025) · Nature · doi:10.1038/s41586-025-09429-6 · Cited by 378 · see citing works

SaProt: Protein Language Modeling with Structure-aware VocabularyPreprint

Su, J., Han, C., Zhou, Y., Shan, J., Zhou, X., & Yuan, F. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.01.560349 · Cited by 251 · see citing works

PADLOC: a web server for the identification of antiviral defence systems in microbial genomes

Payne, L. J., Meaden, S., Mestre, M. R., Palmer, C., Toro, N., Fineran, P. C., & Jackson, S. A. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac400 · Cited by 227 · see citing works

Computational design of serine hydrolases

Lauko, A., Pellock, S. J., Sumida, K. H., Anishchenko, I., Juergens, D., Ahern, W., Jeung, J., Shida, A. F., Hunt, A., Kalvet, I., et al. (2025) · Science · doi:10.1126/science.adu2454 · Cited by 235 · see citing works

Fine-tuning protein language models boosts predictions across diverse tasks

Schmirler, R., Heinzinger, M., & Rost, B. (2024) · Nature Communications · doi:10.1038/s41467-024-51844-2 · Cited by 229 · see citing works

RCSB protein Data Bank: exploring protein 3D similarities via comprehensive structural alignments

Bittrich, S., Segura, J., Duarte, J. M., Burley, S. K., & Rose, Y. (2024) · Bioinformatics · doi:10.1093/bioinformatics/btae370 · Cited by 212 · see citing works

Machine Learning-Guided Protein Engineering

Kouba, P., Kohout, P., Haddadi, F., Bushuiev, A., Samusevich, R., Sedlář, J., Damborský, J., Pluskal, T., Šivic, J., & Mazurenko, S. (2023) · ACS Catalysis · doi:10.1021/acscatal.3c02743 · Cited by 214 · see citing works

Evaluation of AlphaFold-Multimer prediction on multi-chain protein complexes

Zhu, W., Shenoy, A., Kundrotas, P., & Elofsson, A. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad424 · Cited by 202 · see citing works

Language models generalize beyond natural proteins

Verkuil, R., Kabeli, O., Du, Y., Wicky, B. I. M., Milles, L. F., Dauparas, J., Baker, D., Ovchinnikov, S., Sercu, T., & Rives, A. (2022) · doi:10.1101/2022.12.21.521521 · Cited by 181 · see citing works

CASTpFold: Computed Atlas of Surface Topography of the universe of protein Folds

Ye, B., Tian, W., Wang, B., & Liang, J. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae415 · Cited by 180 · see citing works

AlphaFold2 structures guide prospective ligand discovery

Lyu, J., Kapolka, N. J., Gumpper, R. H., Alon, A., Wang, L., Jain, M. K., Barros-Álvarez, X., Sakamoto, K., Kim, Y., DiBerto, J. F., et al. (2024) · Science · doi:10.1126/science.adn6354 · Cited by 182 · see citing works

Uncovering new families and folds in the natural protein universe

Durairaj, J., Waterhouse, A. M., Mets, T., Brodiazhenko, T., Abdullah, M., Studer, G., Tauriello, G., Akdel, M., Andreeva, A. E., Bateman, A. G., et al. (2023) · Nature · doi:10.1038/s41586-023-06622-3 · Cited by 151 · see citing works

Critical assessment of methods of protein structure prediction ( <scp>CASP</scp> )—Round <scp>XV</scp>

Kryshtafovych, A., Schwede, T., Topf, M., Fidelis, K., & Moult, J. (2023) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.26617 · Cited by 148 · see citing works

Template-assisted covalent modification underlies activity of covalent molecular glues

Li, Y.-D., Ma, M. W., Hassan, M. M., Hunkeler, M., Teng, M., Puvar, K., Rutter, J. C., Lumpkin, R. J., Sandoval, B., Jin, C. Y., et al. (2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01668-4 · Cited by 147 · see citing works

What's next for AlphaFold and the AI protein-folding revolution

Callaway, E. (2022) · Nature · doi:10.1038/d41586-022-00997-5 · Cited by 146 · see citing works

Protein remote homology detection and structural alignment using deep learning

Hamamsy, T., Morton, J. T., Blackwell, R., Berenberg, D., Carriero, N. J., Gligorijević, V., Strauss, C. E. M., Leman, J. K., Cho, K., & Bonneau, R. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01917-2 · Cited by 145 · see citing works

An atlas of protein homo-oligomerization across domains of life

Schweke, H., Pacesa, M., Levin, T., Goverde, C. A., Kumar, P., Duhoo, Y., Dornfeld, L. J., Dubreuil, B., Georgeon, S., Ovchinnikov, S., et al. (2024) · Cell · doi:10.1016/j.cell.2024.01.022 · Cited by 144 · see citing works

A <i>Candida auris</i> –specific adhesin, Scf1 <i>,</i> governs surface association, colonization, and virulence

Santana, D. J., Anku, J. A. E., Zhao, G., Zarnowski, R., Johnson, C. J., Hautau, H., Visser, N. D., Ibrahim, A. S., Andes, D., Nett, J. E., et al. (2023) · Science · doi:10.1126/science.adf8972 · Cited by 142 · see citing works

Computational design of soluble and functional membrane protein analogues

Goverde, C. A., Pačesa, M., Goldbach, N. M., Dornfeld, L., Balbi, P. E. M., Georgeon, S., Rosset, S., Kapoor, S., Choudhury, J., Dauparas, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07601-y · Cited by 161 · see citing works

BioLiP2: an updated structure database for biologically relevant ligand–protein interactions

Zhang, C., Zhang, X., Freddolino, L., & Zhang, Y. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad630 · Cited by 142 · see citing works

Prediction of strain level phage-host interactions across the Escherichia genus using only genomic information

Gaborieau, B., Vaysset, H., Tesson, F., Charachon, I., Dib, N., Bernier, J., Dequidt, T., Georjon, H., Clermont, O., Hersen, P., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01832-5 · Cited by 141 · see citing works

Exploring structural diversity across the protein universe with The Encyclopedia of Domains

Lau, A. M., Bordin, N., Kandathil, S. M., Sillitoe, I., Waman, V. P., Wells, J., Orengo, C. A., & Jones, D. T. (2024) · Science · doi:10.1126/science.adq4946 · Cited by 140 · see citing works

Unifying the known and unknown microbial coding sequence space

Vanni, C., Schechter, M. S., Acinas, S. G., Barberán, A., Buttigieg, P. L., Casamayor, E. O., Delmont, T. O., Duarte, C. M., Eren, A. M., Finn, R. D., et al. (2022) · eLife · doi:10.7554/elife.67667 · Cited by 134 · see citing works

A survey of k-mer methods and applications in bioinformatics

Moeckel, C., Mareboina, M., Konnaris, M. A., Chan, C. S. Y., Mouratidis, I., Montgomery, A., Chantzi, N., Pavlopoulos, G. A., & Georgakopoulos-Soares, I. (2024) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2024.05.025 · Cited by 131 · see citing works

AlphaFold2 protein structure prediction: Implications for drug discovery

Borkakoti, N., & Thornton, J. M. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2022.102526 · Cited by 137 · see citing works

The impact of AlphaFold Protein Structure Database on the fields of life sciences

Váradi, M., & Velankar, S. S. (2022) · PROTEOMICS · doi:10.1002/pmic.202200128 · Cited by 132 · see citing works

From sequence to function through structure: Deep learning for protein design

(2022) · doi:10.1016/j.csbj.2022.11.014 · Cited by 124 · see citing works

Protein function prediction as approximate semantic entailment

Kulmanov, M., Guzmán-Vega, F. J., Duek Roggli, P., Lane, L., Arold, S. T., & Hoehndorf, R. (2024) · Nature Machine Intelligence · doi:10.1038/s42256-024-00795-w · Cited by 131 · see citing works

Design of highly functional genome editors by modelling CRISPR–Cas sequences

Ruffolo, J. A., Nayfach, S., Gallagher, J. P., Bhatnagar, A., Beazer, J., Hussain, R., Russ, J., Yip, J., Hill, E., Pačesa, M., et al. (2025) · Nature · doi:10.1038/s41586-025-09298-z · Cited by 212 · see citing works

Atom-level enzyme active site scaffolding using RFdiffusion2

Ahern, W., Yim, J., Tischer, D., Salike, S., Woodbury, S. M., Kim, D., Kalvet, I., Kipnis, Y., Coventry, B., Altae-Tran, H., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02975-x · Cited by 131 · see citing works

Multiple protein structure alignment at scale with FoldMason

Gilchrist, C. L. M., Mirdita, M., & Steinegger, M. (2026) · Science · doi:10.1126/science.ads6733 · Cited by 117 · see citing works

Birth of protein folds and functions in the virome

Nomburg, J., Doherty, E. E., Price, N., Rabelo, D. B., Zhu, Y. K., & Doudna, J. A. (2024) · Nature · doi:10.1038/s41586-024-07809-y · Cited by 117 · see citing works

Site-saturation mutagenesis of 500 human protein domains

Beltran, A., Jiang, X., Shen, Y., & Lehner, B. (2025) · Nature · doi:10.1038/s41586-024-08370-4 · Cited by 126 · see citing works

Data splitting to avoid information leakage with DataSAIL

Joeres, R., Blumenthal, D. B., & Kalinina, O. V. (2025) · Nature Communications · doi:10.1038/s41467-025-58606-8 · Cited by 141 · see citing works

Mirusviruses link herpesviruses to giant viruses

Gaïa, M., Meng, L., Pelletier, E., Forterre, P., Vanni, C., Fernandez-Guerra, A., Jaillon, O., Wincker, P., Ogata, H., Krupovic, M., et al. (2023) · Nature · doi:10.1038/s41586-023-05962-4 · Cited by 108 · see citing works

Genetic manipulation of Patescibacteria provides mechanistic insights into microbial dark matter and the epibiotic lifestyle

Wang, Y., Gallagher, L. A., Andrade, P. A., Liu, A., Humphreys, I. R., Turkarslan, S., Cutler, K. J., Arrieta-Ortiz, M. L., Li, Y., Radey, M. C., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.017 · Cited by 108 · see citing works

Integrating cellular electron microscopy with multimodal data to explore biology across space and time

McCafferty, C. L., Klumpe, S., Amaro, R. E., Kukulski, W., Collinson, L., & Engel, B. D. (2024) · Cell · doi:10.1016/j.cell.2024.01.005 · Cited by 109 · see citing works

Structural phylogenetics unravels the evolutionary diversification of communication systems in gram-positive bacteria and their viruses

Moi, D., Bernard, C., Steinegger, M., Nevers, Y., Langleib, M., & Dessimoz, C. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01649-8 · Cited by 104 · see citing works

AlphaFold2 reveals commonalities and novelties in protein structure space for 21 model organisms

Bordin, N., Sillitoe, I., Nallapareddy, V., Rauer, C., Lam, S. D., Waman, V. P., Sen, N., Heinzinger, M., Littmann, M., Kim, S., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04488-9 · Cited by 103 · see citing works

Functional and evolutionary significance of unknown genes from uncultivated taxa

del Río, Á. R., Giner‐Lamia, J., Cantalapiedra, C. P., Botas, J., Deng, Z., Hernández-Plaza, A., Palmer, M. M., Santamaría‐Hernando, S., Rodríguez‐Herva, J. J., Ruscheweyh, H., et al. (2023) · Nature · doi:10.1038/s41586-023-06955-z · Cited by 110 · see citing works

Computational Approaches to Predict Protein–Protein Interactions in Crowded Cellular Environments

Grassmann, G., Miotto, M., Desantis, F., Rienzo, L. D., Tartaglia, G. G., Pastore, A., Ruocco, G., Monti, M. M., & Milanetti, E. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00550 · Cited by 106 · see citing works

Have protein-ligand cofolding methods moved beyond memorisation?Preprint

Škrinjar, P., Eberhardt, J., Tauriello, G., Schwede, T., & Durairaj, J. (2025) · bioRxiv · doi:10.1101/2025.02.03.636309 · Cited by 100 · see citing works

Genomic language model predicts protein co-regulation and function

Hwang, Y., Cornman, A. L., Kellogg, E. H., Ovchinnikov, S., & Girguis, P. R. (2024) · Nature Communications · doi:10.1038/s41467-024-46947-9 · Cited by 99 · see citing works

The growing repertoire of phage anti-defence systems

Murtazalieva, K., Mu, A., Petrovskaya, A. V., & Finn, R. D. (2024) · Trends in Microbiology · doi:10.1016/j.tim.2024.05.005 · Cited by 99 · see citing works

A Comprehensive Resource for Exploring Antiphage Defense: DefenseFinder Webservice,Wiki and Databases

Tesson, F., Planel, R., Egorov, A. A., Georjon, H., Vaysset, H., Brancotte, B., Néron, B., Mordret, E., Atkinson, G. C., Bernheim, A., et al. (2024) · Peer Community Journal · doi:10.24072/pcjournal.470 · Cited by 120 · see citing works

Sequencing-based analysis of microbiomes

Pinto, Y., & Bhatt, A. S. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00746-6 · Cited by 100 · see citing works

Diverse anti-defence systems are encoded in the leading region of plasmids

Samuel, B., Mittelman, K., Croitoru, S. Y., Haim, M. B., & Burstein, D. (2024) · Nature · doi:10.1038/s41586-024-07994-w · Cited by 90 · see citing works

PLMSearch: Protein language model powers accurate and fast sequence search for remote homology

Liu, W., Wang, Z., You, R., Xie, C., Wei, H., Xiong, Y., Yang, J., & Zhu, S. (2024) · Nature Communications · doi:10.1038/s41467-024-46808-5 · Cited by 96 · see citing works

Extracellular cytochrome nanowires appear to be ubiquitous in prokaryotes

Baquero, D. P., Cvirkaitė‐Krupovič, V., Hu, S. S., Fields, J. L., Liu, X., Rensing, C., Egelman, E. H., Krupovìč, M., & Wang, F. (2023) · Cell · doi:10.1016/j.cell.2023.05.012 · Cited by 90 · see citing works

Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems

Denœud, F., Godfroy, O., Cruaud, C., Heesch, S., Nehr, Z., Tadrent, N., Couloux, A., Brillet-Guéguen, L., Delage, L., Mckeown, D., et al. (2024) · Cell · doi:10.1016/j.cell.2024.10.049 · Cited by 94 · see citing works

Large language models improve annotation of prokaryotic viral proteins

Flamholz, Z. N., Biller, S. J., & Kelly, L. (2024) · Nature Microbiology · doi:10.1038/s41564-023-01584-8 · Cited by 92 · see citing works

An all-atom protein generative model

Chu, A. E., Kim, J., Cheng, L., Nesr, G. E., Xu, M., Shuai, R. W., & Huang, P. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311500121 · Cited by 95 · see citing works

Discovery of FoTO1 and Taxol genes enables biosynthesis of baccatin III

McClune, C. J., Liu, C., Wick, C., Peña, R. D. L., Lange, B. M., Fordyce, P. M., & Sattely, E. S. (2025) · Nature · doi:10.1038/s41586-025-09090-z · Cited by 106 · see citing works

Design of highly functional genome editors by modeling the universe of CRISPR-Cas sequences

Ruffolo, J. A., Nayfach, S., Gallagher, J., Bhatnagar, A., Beazer, J., Hussain, R., Russ, J., Yip, J., Hill, E., Pacesa, M., et al. (2024) · doi:10.1101/2024.04.22.590591 · Cited by 90 · see citing works

RCSB Protein Data Bank: Efficient Searching and Simultaneous Access to One Million Computed Structure Models Alongside the PDB Structures Enabled by Architectural Advances

Bittrich, S., Bhikadiya, C., Bi, C., Chao, H., Duarte, J. M., Dutta, S., Fayazi, M., Henry, J., Khokhriakov, I., Lowe, R., et al. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.167994 · Cited by 83 · see citing works

AI-driven protein design

Koh, H. Y., Zheng, Y., Yang, M., Arora, R., Webb, G. I., Pan, S., Li, L., & Church, G. M. (2025) · Nature Reviews Bioengineering · doi:10.1038/s44222-025-00349-8 · Cited by 96 · see citing works

Generative artificial intelligence for de novo protein design

Winnifrith, A., Outeiral, C., & Hie, B. (2024) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2024.102794 · Cited by 91 · see citing works

GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models of physiological ligand complexes

Herrera, L. P. T., Andreassen, S. N., Caroli, J., Rodríguez‐Espigares, I., Kermani, A. A., Keserű, G. M., Kooistra, A. J., Pándy‐Szekeres, G., & Gloriam, D. E. I. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1065 · Cited by 84 · see citing works

Predicting protein-protein interactions in the human proteome

Zhang, J., Humphreys, I. R., Pei, J., Kim, J., Choi, C., Yuan, R., Durham, J., Liu, S., Choi, H.-J., Baek, M., et al. (2025) · Science · doi:10.1126/science.adt1630 · Cited by 87 · see citing works

Enhancing alphafold-multimer-based protein complex structure prediction with MULTICOM in CASP15

Liu, J., Guo, Z., Wu, T., Roy, R. S., Quadir, F., Chen, C., & Cheng, J. (2023) · Communications Biology · doi:10.1038/s42003-023-05525-3 · Cited by 86 · see citing works

BFVD—a large repository of predicted viral protein structures

Kim, R. S., Levy Karin, E., Mirdita, M., Chikhi, R., & Steinegger, M. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkae1119 · Cited by 86 · see citing works

Enhancing efficiency of protein language models with minimal wet-lab data through few-shot learning

Zhou, Z., Zhang, L., Yu, Y., Wu, B., Li, M., Hong, L., & Tan, P. (2024) · Nature Communications · doi:10.1038/s41467-024-49798-6 · Cited by 89 · see citing works

Accurately predicting enzyme functions through geometric graph learning on ESMFold-predicted structures

Song, Y., Yuan, Q., Chen, S., Zeng, Y., Zhao, H., & Yang, Y. (2024) · Nature Communications · doi:10.1038/s41467-024-52533-w · Cited by 84 · see citing works

Scalable protein design using optimization in a relaxed sequence space

Frank, C., Khoshouei, A., Fuβ, L., Schiwietz, D., Putz, D., Weber, L., Zhao, Z., Hattori, M., Feng, S., de Stigter, Y., et al. (2024) · Science · doi:10.1126/science.adq1741 · Cited by 79 · see citing works

A single NLR gene confers resistance to leaf and stripe rust in wheat

Sharma, D., Avni, R., Gutierrez-Gonzalez, J. J., Kumar, R., Sela, H., Prusty, M. R., Shatil‐Cohen, A., Molnár, I., Holušová, K., Said, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54068-6 · Cited by 87 · see citing works

AlphaFold two years on: Validation and impact

Kovalevskiy, O. V., Mateos-Garcia, J. C., & Tunyasuvunakool, K. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2315002121 · Cited by 81 · see citing works

PLINDER: The protein-ligand interactions dataset and evaluation resourcePreprint

Durairaj, J., Adeshina, Y. O., Cao, Z., Zhang, X., Oleinikovas, V., Duignan, T. J., McClure, Z. D., Robin, X., Studer, G., Kovtun, D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.17.603955 · Cited by 82 · see citing works

Increase in antioxidant capacity associated with the successful subclone of hypervirulent carbapenem-resistant Klebsiella pneumoniae ST11-KL64

Wang, R., Zhang, A., Sun, S., Yin, G., Wu, X., Ding, Q., Wang, Q., Chen, F., Wang, S., van Dorp, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44351-3 · Cited by 78 · see citing works

Structural diversity of axonemes across mammalian motile cilia

Leung, M. R., Sun, C., Zeng, J., Anderson, J. R., Niu, Q., Huang, W., Noteborn, W. E. M., Brown, A., Zeev‐Ben‐Mordehai, T., & Zhang, R. (2025) · Nature · doi:10.1038/s41586-024-08337-5 · Cited by 80 · see citing works

Logan: Planetary-Scale Genome Assembly Surveys Life’s DiversityPreprint

Chikhi, R., Lemane, T., Loll‐Krippleber, R., Montoliu-Nerin, M., Raffestin, B., Camargo, A. P., Miller, C. J., Fiamenghi, M. B., Agustinho, D. P., Majidian, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.30.605881 · Cited by 92 · see citing works

Exploring the diversity of anti-defense systems across prokaryotes, phages and mobile genetic elements

Tesson, F., Huiting, E. D., Wei, L., Ren, J., Johnson, M., Planel, R., Cury, J., Feng, Y., Bondy‐Denomy, J., & Bernheim, A. G. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1171 · Cited by 78 · see citing works

Rapid and sensitive protein complex alignment with Foldseek-Multimer

Kim, W., Mirdita, M., Karin, E. L., Gilchrist, C. L. M., Schweke, H., Söding, J., Levy, E. D., & Steinegger, M. (2025) · Nature Methods · doi:10.1038/s41592-025-02593-7 · Cited by 75 · see citing works

Updated protein domain annotation of the PARP protein family sheds new light on biological function

Suskiewicz, M. J., Munnur, D., Strømland, Ø., Yang, J.-C., Easton, L. E., Chatrin, C., Zhu, K., Baretić, D., Goffinont, S., Schuller, M., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad514 · Cited by 73 · see citing works

Enzymatic polyethylene biorecycling: Confronting challenges and shaping the future

Jin, J., Arciszewski, J., Auclair, K., & Jia, Z. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.132449 · Cited by 78 · see citing works

Diffusion models in protein structure and docking

Yim, J., Stärk, H., Corso, G., Jing, B., Barzilay, R., & Jaakkola, T. (2024) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1711 · Cited by 76 · see citing works

Revolutionizing CRISPR technology with artificial intelligence

Kim, M., Go, M.-J., Kang, S.-H., Jeong, S.-H., & Lim, K. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01462-9 · Cited by 80 · see citing works

Zero-shot prediction of mutation effects with multimodal deep representation learning guides protein engineering

Cheng, P., Mao, C., Tang, J., Yang, S., Cheng, Y., Wang, W., Gu, Q., Han, W., Chen, H., Li, S., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00989-2 · Cited by 76 · see citing works

Viroid-like colonists of human microbiomes

Zheludev, I. N., Edgar, R. C., Lopez-Galiano, M. J., de la Peña, M., Babaian, A., Bhatt, A. S., & Fire, A. Z. (2024) · Cell · doi:10.1016/j.cell.2024.09.033 · Cited by 73 · see citing works

Computational enzyme design by catalytic motif scaffolding

Braun, M., Tripp, A., Chakatok, M., Kaltenbrunner, S., Fischer, C., Stoll, D., Bijelic, A., Elaily, W., Totaro, M. G., Moser, M., et al. (2026) · Nature · doi:10.1038/s41586-025-09747-9 · Cited by 73 · see citing works

Novel machine learning approaches revolutionize protein knowledge

Bordin, N., Dallago, C., Heinzinger, M., Kim, S., Littmann, M., Rauer, C., Steinegger, M., Rost, B., & Orengo, C. (2023) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.11.001 · Cited by 72 · see citing works

GPU-accelerated homology search with MMseqs2

(2025) · doi:10.1038/s41592-025-02819-8 · Cited by 71 · see citing works

Protein structure-informed bacteriophage genome annotation with Phold

Bouras, G., Grigson, S. R., Mirdita, M., Heinzinger, M., Papudeshi, B., Mallawaarachchi, V., Green, R., Kim, R. S., Mihalia, V., Psaltis, A. J., et al. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkaf1448 · Cited by 71 · see citing works

Deep learning for protein structure prediction and design—progress and applications

Jänes, J., & Beltrão, P. (2024) · Molecular Systems Biology · doi:10.1038/s44320-024-00016-x · Cited by 71 · see citing works

Biophysics-based protein language models for protein engineering

Gelman, S., Johnson, B., Freschlin, C. R., Sharma, A., D'Costa, S., Peters, J., Gitter, A., & Romero, P. A. (2025) · Nature Methods · doi:10.1038/s41592-025-02776-2 · Cited by 70 · see citing works

Structure of Geobacter OmcZ filaments suggests extracellular cytochrome polymers evolved independently multiple times

Wang, F., Chan, C. H., Suciu, V., Mustafa, K., Ammend, M., Si, D., Hochbaum, A. I., Egelman, E. H., & Bond, D. R. (2022) · eLife · doi:10.7554/elife.81551 · Cited by 69 · see citing works

Fast methods for protein structure comparison

van Kempen, M. (2026) · doi:10.53846/goediss-12166

Rich structure alphabets enable highest accuracy protein searchPreprint

Edgar, R. C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.24.740611

TM-search: An Efficient and Effective Tool for Protein Structure Database Search

Liu, Z., Zhang, C., Zhang, Q., Zhang, Y., & Yu, D. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01455 · Cited by 10 · see citing works

Foldseek gives AlphaFold protein database a rapid search tool

Hutson, M. (2023) · Nature · doi:10.1038/d41586-023-02205-4 · Cited by 16 · see citing works

Protein structure alignment by Reseek improves sensitivity to remote homologs

Edgar, R. C. (2024) · Bioinformatics · doi:10.1093/bioinformatics/btae687 · Cited by 20 · see citing works