{"doi":"10.1073/pnas.93.24.13665","title":"Energy considerations show that low-barrier hydrogen bonds do not offer a catalytic advantage over ordinary hydrogen bonds","abstract":"<jats:p>\n                    Low-barrier hydrogen bonds have recently been proposed as a major\n factor in enzyme catalysis. Here we evaluate the feasibility of\n transition state (TS) stabilization by low-barrier hydrogen bonds in\n enzymes. Our analysis focuses on the facts that (\n                    <jats:italic>i</jats:italic>\n                    ) a\n low-barrier hydrogen bond is less stable than a regular hydrogen bond\n in water, (\n                    <jats:italic>ii</jats:italic>\n                    ) TSs are more stable in the enzyme active\n sites than in water, and (\n                    <jats:italic>iii</jats:italic>\n                    ) a nonpolar active site\n would destabilize the TS relative to its energy in water. Combining\n these points and other experimental and theoretical facts in a\n physically consistent framework shows that a low-barrier hydrogen bond\n cannot stabilize the TS more than an ordinary hydrogen bond. The reason\n for the large catalytic effect of active site hydrogen bonds is that\n their formation entails a lower reorganization energy than their\n solution counterparts, due to the preorganized enzyme environment.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1996,"id":43742,"datarank":9.884068342389849,"base_score":5.272999558563747,"endowment":5.272999558563747,"self_citation_contribution":0.7909499337845621,"citation_network_contribution":9.093118408605287,"self_endowment_contribution":0.7909499337845621,"citer_contribution":9.093118408605287,"corpus_percentile":null,"corpus_rank":null,"citation_count":194,"citer_count":177,"citers_with_citation_signal":164,"citers_with_endowment":164,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":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":207212,"name":"Arno Papazyan","orcid":null,"position":1,"is_corresponding":false},{"id":128090,"name":"Arieh Warshel","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.272999558563747,"endowment":5.272999558563747,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8942991","pmcid":"PMC19385","openalex_id":"https://openalex.org/W2084953881","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM24492","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM024492","title":null}],"total_grants":2,"fwci":4.1254,"citation_percentile":0.94858638,"influential_citations":1,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":4},{"year":2014,"count":5},{"year":2015,"count":6},{"year":2016,"count":2},{"year":2017,"count":5},{"year":2018,"count":6},{"year":2019,"count":4},{"year":2020,"count":9},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":4}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/19385","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc19385?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/19385","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.93.24.13665","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.93.24.13665","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8942991","host_type":"repository"}],"fields_of_study":["Enzyme Catalysis and Immobilization","Protein Structure and Dynamics","Amino Acid Enzymes and Metabolism","Medicine","Chemistry","Binding Sites","Catalysis","Enzymes","Hydrogen Bonding","Kinetics","Models, Chemical","Models, Structural","Serine Endopeptidases","Static Electricity","Thermodynamics"],"mesh_terms":["Binding Sites","Catalysis","Enzymes","Hydrogen Bonding","Kinetics","Models, Chemical","Models, Structural","Serine Endopeptidases","Thermodynamics","Static Electricity"],"keywords":["Hydrogen bond","Low-barrier hydrogen bond","Chemistry","Catalysis","Hydrogen","Active site","Photochemistry","Molecule","Chemical physics","Computational chemistry","Organic chemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-15T02:53:24.897479Z","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":[]}