One thousand families for the molecular biologist

Profile hidden Markov models

Eddy, S. R. (1998) · Bioinformatics · doi:10.1093/bioinformatics/14.9.755 · Cited by 5,515

STRING v9.1: protein-protein interaction networks, with increased coverage and integration

Franceschini, A., Szklarczyk, D., Frankild, S., Kuhn, M., Simonovic, M., Roth, A., Lin, J., Minguez, P., Bork, P., von Mering, C., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1094 · Cited by 4,398

New families in the classification of glycosyl hydrolases based on amino acid sequence similarities

Henrissat, B., & Bairoch, A. (1993) · Biochemical Journal · doi:10.1042/bj2930781 · Cited by 1,974

Twilight zone of protein sequence alignments

Rost, B. (1999) · Protein Engineering, Design and Selection · doi:10.1093/protein/12.2.85 · Cited by 1,833

Hot Regions in Protein–Protein Interactions: The Organization and Contribution of Structurally Conserved Hot Spot Residues

Keskin, O., Ma, B., & Nussinov, R. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.10.077 · Cited by 519

What is Bioinformatics? A Proposed Definition and Overview of the Field

Luscombe, N. M., Greenbaum, D., & Gerstein, M. (2001) · Methods of Information in Medicine · doi:10.1055/s-0038-1634431 · Cited by 453

What does structure tell us about virus evolution?

Bamford, D. H., Grimes, J. M., & Stuart, D. I. (2005) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2005.10.012 · Cited by 384

Modern proteomes contain putative imprints of ancient shifts in trace metal geochemistry

Dupont, C. L., Yang, S., Palenik, B., & Bourne, P. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605798103 · Cited by 236

Protein Family Expansions and Biological Complexity

Vogel, C., & Chothia, C. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020048 · Cited by 227

Distribution of Protein Folds in the Three Superkingdoms of Life

Wolf, Y. I., Brenner, S. E., Bash, P. A., & Koonin, E. V. (1999) · Genome Research · doi:10.1101/gr.9.1.17 · Cited by 183

Structural space of protein–protein interfaces is degenerate, close to complete, and highly connected

Gao, M., & Skolnick, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012820107 · Cited by 139

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

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

Sequence Variations within Protein Families are Linearly Related to Structural Variations

Koehl, P., & Levitt, M. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00971-3 · Cited by 67

Next Generation Protein Structure Predictions and Genetic Variant Interpretation

Diwan, G. D., Gonzalez-Sanchez, J. C., Apic, G., & Russell, R. B. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167180 · Cited by 30

Introduction

Janin, J., & Wodak, S. J. (2002) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(02)61000-9 · Cited by 31

In silico evolution of globular protein folds from random sequences

Sahakyan, H., Babajanyan, S. G., Wolf, Y. I., & Koonin, E. V. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2509015122 · Cited by 15

Predicting phenotype transition probabilities via conditional algorithmic probability approximations

Dingle, K., Novev, J. K., Ahnert, S. E., & Louis, A. A. (2022) · Journal of the Royal Society Interface · doi:10.1098/rsif.2022.0694 · Cited by 13

Tracing the function expansion for a primordial protein fold in the era of fold-based function prediction: β-trefoil

Goswami, M., & Srinivasan, S. (2025) · PLOS One · doi:10.1371/journal.pone.0320177