{"doi":"10.1128/aac.02823-14","title":"<i>In Vitro</i>\n            and\n            <i>In Vivo</i>\n            Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The\n            <jats:italic>in vivo</jats:italic>\n            antimicrobial activity of DP7 was tested in a\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus</jats:named-content>\n            infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus</jats:named-content>\n            outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2014,"id":596395,"datarank":0.6980940525236285,"base_score":4.653960350157523,"endowment":4.653960350157523,"self_citation_contribution":0.6980940525236285,"citation_network_contribution":0.0,"self_endowment_contribution":0.6980940525236285,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":104,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":533314,"name":"Zhenling Wang","orcid":"0000-0003-0364-8948","position":1,"is_corresponding":false},{"id":326358,"name":"Xiaolu Li","orcid":"0000-0002-9845-1584","position":2,"is_corresponding":false},{"id":1527452,"name":"Yingzi Fan","orcid":null,"position":3,"is_corresponding":false},{"id":686086,"name":"Gu He","orcid":"0000-0002-1536-8882","position":4,"is_corresponding":false},{"id":66395,"name":"Yang Wan","orcid":null,"position":5,"is_corresponding":false},{"id":1527453,"name":"Chaoheng Yu","orcid":null,"position":6,"is_corresponding":false},{"id":1527454,"name":"Jianying Tang","orcid":null,"position":7,"is_corresponding":false},{"id":1093521,"name":"Meng Li","orcid":"0000-0001-8399-8483","position":8,"is_corresponding":false},{"id":678560,"name":"Xian Zhang","orcid":"0000-0001-9156-9742","position":9,"is_corresponding":false},{"id":477138,"name":"Hailong Zhang","orcid":"0000-0002-4903-010X","position":10,"is_corresponding":false},{"id":983257,"name":"Rong Xiang","orcid":"0000-0002-0078-2183","position":11,"is_corresponding":false},{"id":1438034,"name":"Ying Pan","orcid":"0000-0001-9935-6194","position":12,"is_corresponding":false},{"id":418652,"name":"Yan Liu","orcid":"0000-0002-8581-2571","position":13,"is_corresponding":false},{"id":1527456,"name":"Lian Lu","orcid":null,"position":14,"is_corresponding":false},{"id":308327,"name":"Li Yang","orcid":"0000-0001-6589-7195","position":15,"is_corresponding":false},{"id":1527451,"name":"Xiaozhe Wu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>In Vitro</i>\n            and\n            <i>In Vivo</i>\n            Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The\n            <jats:italic>in vivo</jats:italic>\n            antimicrobial activity of DP7 was tested in a\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus</jats:named-content>\n            infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus</jats:named-content>\n            outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.\n          </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24982064","pmcid":"PMC4135812","openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/58/9/5342.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.02823-14","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4135812","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Animals","Mice, Inbred BALB C","Humans","Mice","Gram-Negative Bacteria","Gram-Positive Bacteria","Staphylococcus aureus","Staphylococcal Infections","Amino Acids","Antimicrobial Cationic Peptides","Anti-Infective Agents","Microscopy, Electron","Microbial Sensitivity Tests","Structure-Activity Relationship","Drug Design","Models, Biological","Male"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T10:07:54.422844Z","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":[]}