Molecular docking and ADMET studies of halogenated metabolites from marine sponges as inhibitors of wild-type and mutants PBP2 in Neisseria gonorrhoeae
Gonorrhoea is a sexually transmitted infection (STI) caused by the bacteria . Gonorrhoea symptoms can vary, although roughly 50% of women and 10% of men infected with may be asymptomatic. If left untreated, gonorrhoea can cause major health problems. However, no effective treatment or vaccination is...
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| Published in: | Journal of biomolecular structure & dynamics pp. 1 - 13 |
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| Abstract | Gonorrhoea is a sexually transmitted infection (STI) caused by the bacteria
. Gonorrhoea symptoms can vary, although roughly 50% of women and 10% of men infected with
may be asymptomatic. If left untreated, gonorrhoea can cause major health problems. However, no effective treatment or vaccination is currently available. The enzyme penicillin-binding protein 2 (PBP2) is necessary for cell wall synthesis during
cell growth. The goal of this study is to investigate the molecular interactions of three PBP2 variants with halogenated marine sponge metabolites using molecular docking, molecular dynamic simulation, and ADMET analysis. The docking findings were evaluated using the glide gscore, and the top 20 compounds docked against each PBP2 protein receptor were chosen. Furthermore, the selected compounds underwent ADMET analysis, indicating that they have the potential for therapeutic development. Among the selected compounds, Bromoageliferin had the highest affinity for PBP2, Psammaplysin E for the penicillin-resistant variation of PBP2 protein, and Preaxinellamine for the cephalosporin-resistant variant of PBP2 protein. Additionally, MM-GBSA binding free energy and molecular dynamics simulations were used to support the docking investigations. The results of the study suggest that these compounds may eventually be used to treat gonorrhoea. However, computer validations were included in this study, and more in-vitro research is required to turn these prospective inhibitors into clinical drugs.Communicated by Ramaswamy H. Sarma. |
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| AbstractList | Gonorrhoea is a sexually transmitted infection (STI) caused by the bacteria Neisseria gonorrhoeae. Gonorrhoea symptoms can vary, although roughly 50% of women and 10% of men infected with N. gonorrhoeae may be asymptomatic. If left untreated, gonorrhoea can cause major health problems. However, no effective treatment or vaccination is currently available. The enzyme penicillin-binding protein 2 (PBP2) is necessary for cell wall synthesis during N. gonorrhoeae cell growth. The goal of this study is to investigate the molecular interactions of three PBP2 variants with halogenated marine sponge metabolites using molecular docking, molecular dynamic simulation, and ADMET analysis. The docking findings were evaluated using the glide gscore, and the top 20 compounds docked against each PBP2 protein receptor were chosen. Furthermore, the selected compounds underwent ADMET analysis, indicating that they have the potential for therapeutic development. Among the selected compounds, Bromoageliferin had the highest affinity for PBP2, Psammaplysin E for the penicillin-resistant variation of PBP2 protein, and Preaxinellamine for the cephalosporin-resistant variant of PBP2 protein. Additionally, MM-GBSA binding free energy and molecular dynamics simulations were used to support the docking investigations. The results of the study suggest that these compounds may eventually be used to treat gonorrhoea. However, computer validations were included in this study, and more in-vitro research is required to turn these prospective inhibitors into clinical drugs.Communicated by Ramaswamy H. Sarma. Gonorrhoea is a sexually transmitted infection (STI) caused by the bacteria . Gonorrhoea symptoms can vary, although roughly 50% of women and 10% of men infected with may be asymptomatic. If left untreated, gonorrhoea can cause major health problems. However, no effective treatment or vaccination is currently available. The enzyme penicillin-binding protein 2 (PBP2) is necessary for cell wall synthesis during cell growth. The goal of this study is to investigate the molecular interactions of three PBP2 variants with halogenated marine sponge metabolites using molecular docking, molecular dynamic simulation, and ADMET analysis. The docking findings were evaluated using the glide gscore, and the top 20 compounds docked against each PBP2 protein receptor were chosen. Furthermore, the selected compounds underwent ADMET analysis, indicating that they have the potential for therapeutic development. Among the selected compounds, Bromoageliferin had the highest affinity for PBP2, Psammaplysin E for the penicillin-resistant variation of PBP2 protein, and Preaxinellamine for the cephalosporin-resistant variant of PBP2 protein. Additionally, MM-GBSA binding free energy and molecular dynamics simulations were used to support the docking investigations. The results of the study suggest that these compounds may eventually be used to treat gonorrhoea. However, computer validations were included in this study, and more in-vitro research is required to turn these prospective inhibitors into clinical drugs.Communicated by Ramaswamy H. Sarma. |
| Author | Alajmi, Mohammed F Alanzi, Abdullah R Alqahtani, Moneerah J |
| Author_xml | – sequence: 1 givenname: Abdullah R surname: Alanzi fullname: Alanzi, Abdullah R organization: Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia – sequence: 2 givenname: Mohammed F surname: Alajmi fullname: Alajmi, Mohammed F organization: Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia – sequence: 3 givenname: Moneerah J surname: Alqahtani fullname: Alqahtani, Moneerah J organization: Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38088353$$D View this record in MEDLINE/PubMed |
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| Keywords | Gonorrhoea Neisseria gonorrhoeae molecular docking ADMET penicillin-binding protein 2 |
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| References_xml | – ident: e_1_3_3_45_1 doi: 10.1186/1471-2377-9-S1-S1 – ident: e_1_3_3_16_1 doi: 10.1007/s10822-013-9643-9 – ident: e_1_3_3_34_1 doi: 10.1063/1.1808117 – ident: e_1_3_3_29_1 doi: 10.1155/2005/323082 – ident: e_1_3_3_55_1 – ident: e_1_3_3_53_1 doi: 10.1371/journal.pmed.1002344 – ident: e_1_3_3_47_1 doi: 10.1128/CMR.00010-14 – ident: e_1_3_3_44_1 doi: 10.1021/bi101167x – ident: e_1_3_3_8_1 doi: 10.1002/9780471729259.mc04a02s23 – ident: e_1_3_3_20_1 doi: 10.2174/138920109787048625 – ident: e_1_3_3_38_1 – ident: e_1_3_3_50_1 doi: 10.1128/mBio.01419-18 – ident: e_1_3_3_7_1 doi: 10.1186/s13073-014-0115-1 – ident: e_1_3_3_43_1 doi: 10.1021/bi0350607 – ident: e_1_3_3_49_1 doi: 10.1897/1551-5028(2002)021<2014:SHNPFA>2.0.CO;2 – ident: e_1_3_3_56_1 doi: 10.1128/AAC.00304-09 – ident: e_1_3_3_25_1 doi: 10.2174/1874844901805010012 – ident: e_1_3_3_27_1 doi: 10.1097/OLQ.0000000000001580 – ident: e_1_3_3_37_1 doi: 10.1021/acs.jcim.5b00330 – ident: e_1_3_3_9_1 doi: 10.1021/jm0306430 – ident: e_1_3_3_33_1 doi: 10.1021/jm900776m – ident: e_1_3_3_19_1 doi: 10.1016/j.jmgm.2008.04.001 – ident: e_1_3_3_52_1 doi: 10.1111/j.1365-2958.2008.06424.x – ident: e_1_3_3_10_1 doi: 10.3390/md13074044 – ident: e_1_3_3_6_1 doi: 10.1145/1188455.1188544 – ident: e_1_3_3_24_1 doi: 10.1007/s40265-021-01530-0 – ident: e_1_3_3_26_1 doi: 10.1371/journal.pone.0119264 – volume: 51 start-page: 1293 year: 2011 ident: e_1_3_3_2_1 article-title: Marine compounds and their antimicrobial activities publication-title: Science against Microbial Pathogens: Communicating Current Research and Technological Advances, contributor: fullname: Abad M. J. – volume-title: Omics based approaches for the identification of novel bioactive secondary metabolites from marine sponge derived bacterial isolates year: 2021 ident: e_1_3_3_32_1 contributor: fullname: Patry S. – ident: e_1_3_3_54_1 doi: 10.1007/s11418-021-01557-3 – ident: e_1_3_3_11_1 doi: 10.1126/science.1566067 – ident: e_1_3_3_41_1 doi: 10.1021/ct300203w – ident: e_1_3_3_31_1 doi: 10.1128/AAC.00406-09 – ident: e_1_3_3_21_1 doi: 10.2174/0929867325666181112092159 – volume-title: LigPrep year: 2018 ident: e_1_3_3_22_1 contributor: fullname: LigPrep – ident: e_1_3_3_48_1 doi: 10.1038/s41572-019-0128-6 – ident: e_1_3_3_51_1 doi: 10.1007/s43393-022-00138-z – ident: e_1_3_3_13_1 doi: 10.1021/ci100275a – ident: e_1_3_3_14_1 doi: 10.1128/AAC.49.10.4327-4334.2005 – ident: e_1_3_3_39_1 doi: 10.1371/journal.pone.0220339 – ident: e_1_3_3_12_1 doi: 10.1136/sti.24.4.137 – ident: e_1_3_3_36_1 doi: 10.1021/acs.jctc.7b00028 – ident: e_1_3_3_23_1 doi: 10.3851/IMP3044 – ident: e_1_3_3_17_1 doi: 10.1016/j.toxrep.2022.05.016 – ident: e_1_3_3_40_1 doi: 10.1136/sti.72.6.422 – ident: e_1_3_3_46_1 doi: 10.1071/SH19023 – year: 2012 ident: e_1_3_3_30_1 publication-title: Global Action Plan to Control the Spread and Impact of Antimicrobial Resistance in Neisseria gonorrhoeae contributor: fullname: Organization W. H. – ident: e_1_3_3_4_1 doi: 10.1016/s0140-6736(78)90870-x – ident: e_1_3_3_18_1 doi: 10.1071/SH19061 – ident: e_1_3_3_35_1 doi: 10.1128/mBio.02281-18 – start-page: 131 volume-title: Concepts and experimental protocols of modelling and informatics in drug design year: 2021 ident: e_1_3_3_42_1 doi: 10.1016/B978-0-12-820546-4.00006-4 contributor: fullname: Silakari O. – ident: e_1_3_3_3_1 doi: 10.1128/AAC.46.12.3744-3749.2002 – volume: 12 start-page: 881392 year: 2022 ident: e_1_3_3_28_1 article-title: Recent progress towards a gonococcal vaccine publication-title: Frontiers in Cellular and Infection Microbiology doi: 10.3389/fcimb.2022.881392 contributor: fullname: Maurakis S. A. – ident: e_1_3_3_5_1 doi: 10.1136/sti.2006.023036 – ident: e_1_3_3_15_1 doi: 10.1517/14728214.7.2.223 |
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| Snippet | Gonorrhoea is a sexually transmitted infection (STI) caused by the bacteria
. Gonorrhoea symptoms can vary, although roughly 50% of women and 10% of men... Gonorrhoea is a sexually transmitted infection (STI) caused by the bacteria Neisseria gonorrhoeae. Gonorrhoea symptoms can vary, although roughly 50% of women... |
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| Title | Molecular docking and ADMET studies of halogenated metabolites from marine sponges as inhibitors of wild-type and mutants PBP2 in Neisseria gonorrhoeae |
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