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References from Graph-based representations in modern protein science. Local targets link to admitted publications; unresolved targets remain external evidence.
Small-world communication of residues and significance for protein dynamics
10.1016/s0006-3495(04)74086-2 · 2004 · External reference
Genotype networks shed light on evolutionary constraints
10.1016/j.tree.2011.07.001 · 2011 · External reference
Using sequence similarity networks for visualization of relationships across diverse protein superfamilies
10.1371/journal.pone.0004345 · 2009 · External reference
Network biology: understanding the cell’s functional organization
10.1038/nrg1272 · 2004 · External reference
Protein contact networks: an emerging paradigm in chemistry
10.1021/cr3002356 · 2013 · External reference
Residues crucial for maintaining short paths in network communication mediate signaling in proteins
10.1038/msb4100063 · 2006 · External reference
Evolution and engineering of allosteric regulation in protein kinases
10.1126/scisignal.aar3250 · 2018 · External reference
Darwinian evolution can follow only very few mutational paths to fitter proteins
10.1126/science.1123539 · 2006 · External reference
Evolutionary accessibility of mutational pathways
10.1371/journal.pcbi.1002134 · 2011 · External reference
Empirical fitness landscapes and the predictability of evolution
10.1038/nrg3744 · 2014 · External reference
Connectivity between catalytic landscapes of the metallo-β-lactamase superfamily
10.1016/j.jmb.2014.04.013 · 2014 · External reference
Exploring large protein sequence space through homology- and representation-based hierarchical clustering
10.1093/molbev/msaf136 · 2025 · External reference
Central dogma of molecular biology
10.1038/227561a0 · 1970 · External reference
A general method applicable to the search for similarities in the amino acid sequence of two proteins
10.1016/0022-2836(70)90057-4 · 1970 · External reference
A model of evolutionary change in proteins
1978 · External reference
Basic local alignment search tool
10.1016/s0022-2836(05)80360-2 · 1990 · External reference
Highly accurate protein structure prediction with AlphaFold
10.1038/s41586-021-03819-2 · 2021 · External reference
Direct-coupling analysis of residue coevolution captures native contacts across many protein families
10.1073/pnas.1111471108 · 2011 · External reference
Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences
10.1073/pnas.2016239118 · 2021 · External reference
Evolutionary trees from DNA sequences: a maximum likelihood approach
10.1007/bf01734359 · 1981 · External reference
Mutation effects predicted from sequence co-variation
10.1038/nbt.3769 · 2017 · External reference
Improved inference of intermolecular contacts through protein–protein interaction prediction using coevolutionary analysis
10.1093/bioinformatics/bty924 · 2019 · External reference
MSA transformer
2021 · External reference
Epistasis in protein evolution
10.1002/pro.2897 · 2016 · External reference
Principles that govern the folding of protein chains
10.1126/science.181.4096.223 · 1973 · External reference
Funnels, pathways, and the energy landscape of protein folding: a synthesis
10.1002/prot.340210302 · 1995 · External reference
LM-GVP: an extensible sequence and structure informed deep learning framework for protein property prediction
10.1038/s41598-022-10775-y · 2022 · External reference
Unsupervised evolution of protein and antibody complexes with a structure-informed language model
10.1126/science.adk8946 · 2024 · External reference
SSEmb: a joint embedding of protein sequence and structure enables robust variant effect predictions
10.1038/s41467-024-53982-z · 2024 · External reference
A comprehensive phylogenetic analysis of the serpin superfamily
10.1093/molbev/msab081 · 2021 · External reference
Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade
10.7554/elife.79790 · 2022 · External reference
Analysis of insertions and extensions in the functional evolution of the ribonucleotide reductase family
10.1002/pro.4483 · 2022 · External reference
Robust deep learning-based protein sequence design using ProteinMPNN
10.1126/science.add2187 · 2022 · External reference
Exploring network structure, dynamics, and function using NetworkX
10.25080/tcwv9851 · 2008 · External reference
MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets
10.1038/nbt.3988 · 2017 · External reference
Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): a web tool for generating protein sequence similarity networks
10.1016/j.bbapap.2015.04.015 · 2015 · External reference
Cytoscape: a software environment for integrated models of biomolecular interaction networks
10.1101/gr.1239303 · 2003 · External reference
IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era
10.1093/molbev/msaa015 · 2020 · External reference
IQ-TREE 3: phylogenomic inference software using complex evolutionary models
10.1093/molbev/msag117 · 2026 · External reference
BEAST 2.5: an advanced software platform for Bayesian evolutionary analysis
10.1371/journal.pcbi.1006650 · 2019 · External reference
RING 4.0: faster residue interaction networks with novel interaction types across over 35,000 different chemical structures
10.1093/nar/gkae337 · 2024 · External reference
NAPS: network analysis of protein structures
10.1093/nar/gkw383 · 2016 · External reference
The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest
10.1093/nar/gkac1000 · 2023 · External reference
The BioGRID database: a comprehensive biomedical resource of curated protein, genetic, and chemical interactions
10.1002/pro.3978 · 2021 · External reference
The IntAct database: efficient access to fine-grained molecular interaction data
10.1093/nar/gkab1006 · 2022 · External reference
The Reactome Pathway Knowledgebase 2024
10.1093/nar/gkad1025 · 2024 · External reference
Gene Ontology Causal Activity Modeling (GO-CAM) moves beyond GO annotations to structured descriptions of biological functions and systems
10.1038/s41588-019-0500-1 · 2019 · External reference
KG-Hub—building and exchanging biological knowledge graphs
10.1093/bioinformatics/btad418 · 2023 · External reference
Fast graph representation learning with PyTorch geometric
10.48550/arxiv.1903.02428 · 2019 · External reference
Deep graph library: a graph-centric, highly-performant package for graph neural networks
10.48550/arxiv.1909.01315 · 2019 · External reference
De novo design of protein structure and function with RFdiffusion
10.1038/s41586-023-06415-8 · 2023 · External reference
Natural selection and the concept of a protein space
10.1038/225563a0 · 1970 · External reference
The roles of mutation, inbreeding, crossbreeding and selection in evolution
1932 · External reference
The structure of genotype-phenotype maps makes fitness landscapes navigable
10.1038/s41559-022-01867-z · 2022 · External reference
Predicting the topography of fitness landscapes from the structure of genotype-phenotype maps
10.1093/genetics/iyag026 · 2026 · External reference
A rugged yet easily navigable fitness landscape
10.1126/science.adh3860 · 2023 · External reference
Evolutionary Rate at the Molecular Level
10.1038/217624a0 · 1968 · External reference
Non-Darwinian evolution
10.1126/science.164.3881.788 · 1969 · External reference
From sequences to shapes and back: a case study in RNA secondary structures
10.1098/rspb.1994.0040 · 1994 · External reference
Generic properties of combinatory maps: neutral networks of RNA secondary structures
10.1007/bf02462007 · 1997 · External reference
Modeling evolutionary landscapes: mutational stability, topology, and superfunnels in sequence space
10.1073/pnas.96.19.10689 · 1999 · External reference
Why are proteins marginally stable?
10.1002/prot.10016 · 2002 · External reference
Protein stability promotes evolvability
10.1073/pnas.0510098103 · 2006 · External reference
Evolution and speciation on holey adaptive landscapes
10.1016/s0169-5347(97)01098-7 · 1997 · External reference
Percolation on the fitness hypercube and the evolution of reproductive isolation
10.1006/jtbi.1996.0242 · 1997 · External reference
Synonymous codon substitutions perturb cotranslational protein folding in vivo and impair cell fitness
10.1073/pnas.1907126117 · 2020 · External reference
Synonymous but not silent: the codon usage code for gene expression and protein folding
10.1146/annurev-biochem-071320-112701 · 2021 · External reference
Experimental exploration of a ribozyme neutral network using evolutionary algorithm and deep learning
10.1038/s41467-022-32538-z · 2022 · External reference
Robustness and innovation in synthetic genotype networks
10.1038/s41467-023-38033-3 · 2023 · External reference
Mapping protein neutral networks from predicted secondary structure
10.64898/2026.03.04.709605 · 2026 · External reference
Neutral quasispecies evolution and the maximal entropy random walk
10.1126/sciadv.abb2376 · 2021 · External reference
Neutral evolution of mutational robustness
10.1073/pnas.96.17.9716 · 1999 · External reference
Evolution favors protein mutational robustness in sufficiently large populations
10.1186/1741-7007-5-29 · 2007 · External reference
Robustness, evolvability, and neutrality
10.1016/j.febslet.2005.01.063 · 2005 · External reference
The “evolvability” of promiscuous protein functions
10.1038/ng1482 · 2005 · External reference
Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein
10.1038/nature05385 · 2006 · External reference
Stability effects of mutations and protein evolvability
10.1016/j.sbi.2009.08.003 · 2009 · External reference
Uncovering cryptic genetic variation
10.1038/nrg1426 · 2004 · External reference
Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes
10.7554/elife.40789 · 2019 · External reference
Historical contingency and its biophysical basis in glucocorticoid receptor evolution
10.1038/nature13410 · 2014 · External reference
Crystal structure of an ancient protein: evolution by conformational epistasis
10.1126/science.1142819 · 2007 · External reference
Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme
10.1038/s41589-019-0386-3 · 2019 · External reference
The biochemical architecture of an ancient adaptive landscape
10.1126/science.1115649 · 2005 · External reference
Adaptation in protein fitness landscapes is facilitated by indirect paths
10.7554/elife.16965 · 2016 · External reference
The highly rugged yet navigable regulatory landscape of the bacterial transcription factor TetR
10.1038/s41467-024-54723-y · 2024 · External reference
A combinatorially complete epistatic fitness landscape in an enzyme active site
10.1073/pnas.2400439121 · 2024 · External reference
Network of epistatic interactions in an enzyme active site revealed by large-scale deep mutational scanning
10.1073/pnas.2313513121 · 2024 · External reference
Epistatic hotspots organize antibody fitness landscape and boost evolvability
10.1073/pnas.2413884122 · 2025 · External reference
Reverse evolution leads to genotypic incompatibility despite functional and active site convergence
10.7554/elife.06492 · 2015 · External reference
Enriching productive mutational paths accelerates enzyme evolution
10.1038/s41589-024-01712-3 · 2024 · External reference
Increasing the soluble expression and whole-cell activity of the plastic-degrading enzyme MHETase through consensus design
10.1021/acs.biochem.4c00165 · 2024 · External reference
Experimental illumination of a fitness landscape
10.1073/pnas.1016024108 · 2011 · External reference
Stability-mediated epistasis constrains the evolution of an influenza protein
10.7554/elife.00631 · 2013 · External reference
Local fitness landscape of the green fluorescent protein
10.1038/nature17995 · 2016 · External reference
Investigating the determinants of performance in machine learning for protein fitness prediction
10.1002/pro.70235 · 2025 · External reference
Towards a general theory of adaptive walks on rugged landscapes
10.1016/s0022-5193(87)80029-2 · 1987 · External reference
Epistasis and adaptation on fitness landscapes
10.1146/annurev-ecolsys-102320-112153 · 2022 · External reference
Computational and experimental exploration of protein fitness landscapes: navigating smooth and rugged terrains
10.1021/acs.biochem.4c00673 · 2025 · External reference
Empirical fitness landscapes reveal accessible evolutionary paths
10.1038/nature05451 · 2007 · External reference
Unbiased inference of the fitness landscape ruggedness from imprecise fitness estimates
10.1111/evo.14363 · 2021 · External reference
Perspective: sign epistasis and genetic constraint on evolutionary trajectories
10.1111/j.0014-3820.2005.tb01768.x · 2005 · External reference
Correlated and uncorrelated fitness landscapes and how to tell the difference
10.1007/bf00202749 · 1990 · External reference
Exploring the complexity of the HIV-1 fitness landscape
10.1371/journal.pgen.1002551 · 2012 · External reference
Landscapes and their correlation functions
10.1007/bf01165154 · 1995 · External reference
Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors
10.1016/j.cels.2024.03.002 · 2024 · External reference
Leveraging ancestral sequence reconstruction for protein representation learning
10.1038/s42256-024-00935-2 · 2024 · External reference
Ancestral reconstruction of polyethylene terephthalate degrading cutinases reveals a rugged and unexplored sequence-fitness landscape
10.1126/sciadv.ads8318 · 2025 · External reference
Protein fitness landscape: spectral graph theory perspective
2025 · External reference
Discrete signal processing on graphs: frequency analysis
10.1109/tsp.2014.2321121 · 2014 · External reference
Exact results for amplitude spectra of fitness landscapes
10.1016/j.jtbi.2013.05.002 · 2013 · External reference
The NK model of rugged fitness landscapes and its application to maturation of the immune response
10.1016/s0022-5193(89)80019-0 · 1989 · External reference
Universality classes of interaction structures for NK fitness landscapes
10.1007/s10955-018-1979-z · 2018 · External reference
Analysis of a local fitness landscape with a model of the rough Mt. Fuji-type landscape: application to prolyl endopeptidase and thermolysin
10.1002/(sici)1097-0282(200007)54:1<64::aid-bip70>3.0.co;2-r · 2000 · External reference
Measuring epistasis in fitness landscapes: the correlation of fitness effects of mutations
10.1016/j.jtbi.2016.01.037 · 2016 · External reference
Evolutionary consequences of selected locus-specific variations in epistasis and fitness contribution in Kauffman's NK model
10.1006/jtbi.1998.0832 · 1999 · External reference
A comparison of neutral landscapes—NK, NKp and NKq
2002 · External reference
On the sparsity of fitness functions and implications for learning
10.1073/pnas.2109649118 · 2022 · External reference
Accessibility of modified NK fitness landscapes
10.48550/arxiv.2512.15828 · 2025 · External reference
Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies
10.1007/s10969-008-9056-5 · 2009 · External reference
Experimental strategies for functional annotation and metabolism discovery: targeted screening of solute binding proteins and unbiased panning of metabolomes
10.1021/bi501388y · 2015 · External reference
Sequence-structure-function classification of a catalytically diverse oxidoreductase superfamily in Mycobacteria
10.1016/j.jmb.2015.09.021 · 2015 · External reference
Revealing unexplored sequence-function space using sequence similarity networks
10.1021/acs.biochem.8b00473 · 2018 · External reference
A global view of structure-function relationships in the tautomerase superfamily
10.1074/jbc.m117.815340 · 2018 · External reference
Atlas of the radical SAM superfamily: divergent evolution of function using a “plug and play” domain
10.1016/bs.mie.2018.06.004 · 2018 · External reference
Bioinformatic analysis of the flavin-dependent amine oxidase superfamily: adaptations for substrate specificity and catalytic diversity
10.1016/j.jmb.2020.03.007 · 2020 · External reference
Widespread promiscuous alkaline phosphatases underscore ancient microbial phosphite utilization
10.1073/pnas.2513042122 · 2025 · External reference
Combining phylogeny and coevolution improves the inference of interaction partners among paralogous proteins
10.1371/journal.pcbi.1011010 · 2023 · External reference
Ancestral sequence reconstructions of MotB are proton-motile and require MotA for motility
10.3389/fmicb.2020.625837 · 2020 · External reference
Panoramic view of a superfamily of phosphatases through substrate profiling
10.1073/pnas.1423570112 · 2015 · External reference
Identification and characterization of a bacterial periplasmic solute binding protein that binds l-amino acid amides
10.1021/acs.biochem.4c00096 · 2024 · External reference
Uncovering new families and folds in the natural protein universe
10.1038/s41586-023-06622-3 · 2023 · External reference
EFI-EST, EFI-GNT, and EFI-CGFP: enzyme function initiative (EFI) web resource for genomic enzymology tools
10.1016/j.jmb.2023.168018 · 2023 · External reference
Small-world view of the amino acids that play a key role in protein folding
10.1103/physreve.65.061910 · 2002 · External reference
Collective dynamics of ‘small-world’ networks
10.1038/30918 · 1998 · External reference
Network analysis of protein structures identifies functional residues
10.1016/j.jmb.2004.10.055 · 2004 · External reference
The origin of allosteric functional modulation: multiple pre-existing pathways
10.1016/j.str.2009.06.008 · 2009 · External reference
Evolutionarily conserved pathways of energetic connectivity in protein families
10.1126/science.286.5438.295 · 1999 · External reference
Evolutionarily conserved networks of residues mediate allosteric communication in proteins
10.1038/nsb881 · 2003 · External reference
The spatial architecture of protein function and adaptation
10.1038/nature11500 · 2012 · External reference
Protein sectors: evolutionary units of three-dimensional structure
10.1016/j.cell.2009.07.038 · 2009 · External reference
Protein sectors: statistical coupling analysis versus conservation
10.1371/journal.pcbi.1004091 · 2015 · External reference
Origins of coevolution between residues distant in protein 3D structures
10.1073/pnas.1702664114 · 2017 · External reference
Allostery without conformational change. A plausible model
10.1007/bf00276625 · 1984 · External reference
Dynamical networks in tRNA:protein complexes
10.1073/pnas.0810961106 · 2009 · External reference
Evolutionary rewiring of the dynamic network underpinning allosteric epistasis in NS1 of the influenza A virus
10.1073/pnas.2410813122 · 2025 · External reference
Lethality and centrality in protein networks
10.1038/35075138 · 2001 · External reference
Scale-free networks are rare
10.1038/s41467-019-08746-5 · 2019 · External reference
Emergence of power law distributions in protein–protein interaction networks through study bias
10.7554/elife.99951 · 2024 · External reference
Error and attack tolerance of complex networks
10.1038/35019019 · 2000 · External reference
Why do hubs in the yeast protein interaction network tend to be essential: reexamining the connection between the network topology and essentiality
10.1371/journal.pcbi.1000140 · 2008 · External reference
From molecular to modular cell biology
10.1038/35011540 · 1999 · External reference
An efficient algorithm for large-scale detection of protein families
10.1093/nar/30.7.1575 · 2002 · External reference
Network pharmacology: the next paradigm in drug discovery
10.1038/nchembio.118 · 2008 · External reference
Widespread macromolecular interaction perturbations in human genetic disorders
10.1016/j.cell.2015.04.013 · 2015 · External reference
Geometric deep learning: grids, groups, graphs, geodesics, and gauges
10.48550/arxiv.2104.13478 · 2021 · External reference
SE(3) equivariant graph neural networks with complete local frames
2022 · External reference
Geometricus represents protein structures as shape-mers derived from moment invariants
10.1093/bioinformatics/btaa839 · 2020 · External reference
Accurate structure prediction of biomolecular interactions with AlphaFold 3
10.1038/s41586-024-07487-w · 2024 · External reference
Accurate prediction of protein structures and interactions using a three-track neural network
10.1126/science.abj8754 · 2021 · External reference
Evolutionary-scale prediction of atomic-level protein structure with a language model
10.1126/science.ade2574 · 2023 · External reference
Generalized biomolecular modeling and design with RoseTTAFold All-Atom
10.1126/science.adl2528 · 2024 · External reference
Accelerating biomolecular modeling with AtomWorks and RF3
10.1101/2025.08.14.670328 · 2025 · External reference
Inverted protein structure prediction
10.1016/s0959-440x(05)80118-6 · 1993 · External reference
A method to identify protein sequences that fold into a known three-dimensional structure
10.1126/science.1853201 · 1991 · External reference
Atomic context-conditioned protein sequence design using LigandMPNN
10.1038/s41592-025-02626-1 · 2025 · External reference
Computational design of soluble and functional membrane protein analogues
10.1038/s41586-024-07601-y · 2024 · External reference
Mixture of experts enable efficient and effective protein understanding and design
10.1101/2024.11.29.625425 · 2024 · External reference
Retrieval augmented protein language models for protein structure prediction
10.1101/2024.12.02.626519 · 2024 · External reference
Transformer-based protein generation with regularized latent space optimization
10.1038/s42256-022-00532-1 · 2022 · External reference
Epistatic Net allows the sparse spectral regularization of deep neural networks for inferring fitness functions
10.1038/s41467-021-25371-3 · 2021 · External reference
UniProt: the Universal Protein Knowledgebase in 2025
10.1093/nar/gkae1010 · 2025 · External reference
Neuro-symbolic representation learning on biological knowledge graphs
10.1093/bioinformatics/btx275 · 2017 · External reference
Guilt-by-association goes global
10.1038/35001165 · 2000 · External reference
Biomedical knowledge graph learning for drug repurposing by extending guilt-by-association to multiple layers
10.1038/s41467-023-39301-y · 2023 · External reference
“Guilt by association” is the exception rather than the rule in gene networks
10.1371/journal.pcbi.1002444 · 2012 · External reference
Training compute-optimal protein language models
10.52202/079017-2216 · 2024 · External reference
Petabase-scale homology search for structure prediction
10.1101/cshperspect.a041465 · 2024 · External reference
GPU-accelerated homology search with MMseqs2
10.1038/s41592-025-02819-8 · 2025 · External reference
Efficient and accurate search in petabase-scale sequence repositories
10.1038/s41586-025-09603-w · 2025 · External reference
node2vec: scalable feature learning for networks
10.1145/2939672.2939754 · 2016 · External reference
Fast protein structure searching using structure graph embeddings
10.1093/bioadv/vbaf042 · 2025 · External reference
Fast and accurate protein structure search with Foldseek
10.1038/s41587-023-01773-0 · 2024 · External reference
Resurrecting ancient genes: experimental analysis of extinct molecules
10.1038/nrg1324 · 2004 · External reference
Variant evolution graph: can we infer how SARS-CoV-2 variants are evolving?
10.1371/journal.pone.0323970 · 2025 · External reference
Evolutionary velocity with protein language models predicts evolutionary dynamics of diverse proteins
10.1016/j.cels.2022.01.003 · 2022 · External reference
Machine-learning-guided directed evolution for protein engineering
10.1038/s41592-019-0496-6 · 2019 · External reference
Protein evolution as a complex system
10.1038/s41589-025-01977-2 · 2025 · External reference