{"doi":"10.1093/protein/gzab009","title":"The evolution and engineering of enzyme activity through tuning conformational landscapes","abstract":"<jats:title>Abstract</jats:title><jats:p>Proteins are dynamic molecules whose structures consist of an ensemble of conformational states. Dynamics contribute to protein function and a link to protein evolution has begun to emerge. This increased appreciation for the evolutionary impact of conformational sampling has grown from our developing structural biology capabilities and the exploration of directed evolution approaches, which have allowed evolutionary trajectories to be mapped. Recent studies have provided empirical examples of how proteins can evolve via conformational landscape alterations. Moreover, minor conformational substates have been shown to be involved in the emergence of new enzyme functions as they can become enriched through evolution. The role of remote mutations in stabilizing new active site geometries has also granted insight into the molecular basis underpinning poorly understood epistatic effects that guide protein evolution. Finally, we discuss how the growth of our understanding of remote mutations is beginning to refine our approach to engineering enzymes.</jats:p>","journal":"Protein Engineering, Design and Selection","year":2021,"id":46665,"datarank":0.9113804018587224,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.3869042676387503,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.3869042676387503,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":31,"citers_with_citation_signal":19,"citers_with_endowment":19,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":216039,"name":"Colin J Jackson","orcid":null,"position":1,"is_corresponding":false},{"id":216038,"name":"Adam M Damry","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The evolution and engineering of enzyme activity through tuning conformational landscapes","abstract":"<jats:title>Abstract</jats:title><jats:p>Proteins are dynamic molecules whose structures consist of an ensemble of conformational states. Dynamics contribute to protein function and a link to protein evolution has begun to emerge. This increased appreciation for the evolutionary impact of conformational sampling has grown from our developing structural biology capabilities and the exploration of directed evolution approaches, which have allowed evolutionary trajectories to be mapped. Recent studies have provided empirical examples of how proteins can evolve via conformational landscape alterations. Moreover, minor conformational substates have been shown to be involved in the emergence of new enzyme functions as they can become enriched through evolution. The role of remote mutations in stabilizing new active site geometries has also granted insight into the molecular basis underpinning poorly understood epistatic effects that guide protein evolution. Finally, we discuss how the growth of our understanding of remote mutations is beginning to refine our approach to engineering enzymes.</jats:p>","is_dataset_classified":null,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33903911","pmcid":null,"openalex_id":"https://openalex.org/W3158684549","authors":[],"funders":[{"funder_name":"Human Frontier Science Program","grant_id":"LT000366/2020","title":null},{"funder_name":"Peptide and Protein Science","grant_id":"CE200100012","title":null},{"funder_name":"Australian Research Council Centres of Excellence in Synthetic Biology","grant_id":"CE200100029","title":null}],"total_grants":3,"fwci":2.0353,"citation_percentile":0.8739201,"influential_citations":0,"citation_trend":[{"year":2022,"count":7},{"year":2023,"count":10},{"year":2024,"count":8},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"closed","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"http://academic.oup.com/peds/article-pdf/doi/10.1093/protein/gzab009/37405569/gzab009.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/protein/gzab009","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33903911","host_type":"repository"},{"url":"http://hdl.handle.net/1885/315702","host_type":"repository"}],"fields_of_study":["Protein Structure and Dynamics","Microbial Metabolic Engineering and Bioproduction","Microbial Natural Products and Biosynthesis","Medicine","Engineering","Biology","Chemistry","Catalytic Domain","Evolution, Molecular","Mutation","Protein Conformation","Proteins"],"mesh_terms":["Mutation","Protein Conformation","Proteins","Evolution, Molecular","Catalytic Domain"],"keywords":["Epistasis","Protein engineering","Directed evolution","Directed Molecular Evolution","Conformational ensembles","Protein function","Protein evolution","Molecular dynamics","Function (biology)","Protein structure","Conformational change","Molecular evolution","Computational biology","Biology","Evolutionary biology","Enzyme","Biophysics","Chemistry","Biochemistry","Phylogenetics","Computational chemistry","protein dynamics","Enzyme Engineering","Enzyme Evolution","Enzyme Conformational Landscapes"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-13T00:30:01.190199Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}