A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling
Abstract Lactate dehydrogenase (LDH) is a tetramer enzyme that converts pyruvate to lactate reversibly. This enzyme becomes important because it is associated with diseases such as cancers, heart disease, liver problems, and most importantly, corona disease. As a system-based method, proteochemometr...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-07-01
|
| Series: | BMC Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13065-023-00991-6 |
| _version_ | 1797784758255616000 |
|---|---|
| author | Sedigheh Damavandi Fereshteh Shiri Abbasali Emamjomeh Somayeh Pirhadi Hamid Beyzaei |
| author_facet | Sedigheh Damavandi Fereshteh Shiri Abbasali Emamjomeh Somayeh Pirhadi Hamid Beyzaei |
| author_sort | Sedigheh Damavandi |
| collection | DOAJ |
| description | Abstract Lactate dehydrogenase (LDH) is a tetramer enzyme that converts pyruvate to lactate reversibly. This enzyme becomes important because it is associated with diseases such as cancers, heart disease, liver problems, and most importantly, corona disease. As a system-based method, proteochemometrics does not require knowledge of the protein's three-dimensional structure, but rather depends on the amino acid sequence and protein descriptors. Here, we applied this methodology to model a set of LDHA and LDHB isoenzyme inhibitors. To implement the proteochemetrics method, the camb package in the R Studio Server programming environment was used. The activity of 312 compounds of LDHA and LDHB isoenzyme inhibitors from the valid Binding DB database was retrieved. The proteochemometrics method was applied to three machine learning algorithms gradient amplification model, random forest, and support vector machine as regression methods to find the best model. Through the combination of different models into an ensemble (greedy and stacking optimization), we explored the possibility of improving the performance of models. For the RF best ensemble model of inhibitors of LDHA and LDHB isoenzymes, and were 0.66 and 0.62, respectively. LDH inhibitory activation is influenced by Morgan fingerprints and topological structure descriptors. |
| first_indexed | 2024-03-13T00:44:27Z |
| format | Article |
| id | doaj.art-5489717fd3944dadb59d736082259254 |
| institution | Directory Open Access Journal |
| issn | 2661-801X |
| language | English |
| last_indexed | 2024-03-13T00:44:27Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj.art-5489717fd3944dadb59d7360822592542023-07-09T11:05:11ZengBMCBMC Chemistry2661-801X2023-07-0117111310.1186/s13065-023-00991-6A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modelingSedigheh Damavandi0Fereshteh Shiri1Abbasali Emamjomeh2Somayeh Pirhadi3Hamid Beyzaei4Department of Bioinformatics, Laboratory of Computational Biotechnology and Bioinformatics (CBB Lab), University of ZabolDepartment of Chemistry, Faculty of Science, University of ZabolDepartment of Bioinformatics, Laboratory of Computational Biotechnology and Bioinformatics (CBB Lab), University of ZabolMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesDepartment of Chemistry, Faculty of Science, University of ZabolAbstract Lactate dehydrogenase (LDH) is a tetramer enzyme that converts pyruvate to lactate reversibly. This enzyme becomes important because it is associated with diseases such as cancers, heart disease, liver problems, and most importantly, corona disease. As a system-based method, proteochemometrics does not require knowledge of the protein's three-dimensional structure, but rather depends on the amino acid sequence and protein descriptors. Here, we applied this methodology to model a set of LDHA and LDHB isoenzyme inhibitors. To implement the proteochemetrics method, the camb package in the R Studio Server programming environment was used. The activity of 312 compounds of LDHA and LDHB isoenzyme inhibitors from the valid Binding DB database was retrieved. The proteochemometrics method was applied to three machine learning algorithms gradient amplification model, random forest, and support vector machine as regression methods to find the best model. Through the combination of different models into an ensemble (greedy and stacking optimization), we explored the possibility of improving the performance of models. For the RF best ensemble model of inhibitors of LDHA and LDHB isoenzymes, and were 0.66 and 0.62, respectively. LDH inhibitory activation is influenced by Morgan fingerprints and topological structure descriptors.https://doi.org/10.1186/s13065-023-00991-6ProteochemometricsMachine learning algorithmIsoenzymeCamb packageMorgan fingerprints |
| spellingShingle | Sedigheh Damavandi Fereshteh Shiri Abbasali Emamjomeh Somayeh Pirhadi Hamid Beyzaei A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling BMC Chemistry Proteochemometrics Machine learning algorithm Isoenzyme Camb package Morgan fingerprints |
| title | A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling |
| title_full | A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling |
| title_fullStr | A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling |
| title_full_unstemmed | A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling |
| title_short | A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling |
| title_sort | study of the interaction space of two lactate dehydrogenase isoforms ldha and ldhb and some of their inhibitors using proteochemometrics modeling |
| topic | Proteochemometrics Machine learning algorithm Isoenzyme Camb package Morgan fingerprints |
| url | https://doi.org/10.1186/s13065-023-00991-6 |
| work_keys_str_mv | AT sedighehdamavandi astudyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT fereshtehshiri astudyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT abbasaliemamjomeh astudyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT somayehpirhadi astudyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT hamidbeyzaei astudyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT sedighehdamavandi studyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT fereshtehshiri studyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT abbasaliemamjomeh studyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT somayehpirhadi studyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling AT hamidbeyzaei studyoftheinteractionspaceoftwolactatedehydrogenaseisoformsldhaandldhbandsomeoftheirinhibitorsusingproteochemometricsmodeling |