{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:38:24Z","timestamp":1772210304424,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taif University, Saudi Arabia","award":["TU-DSPP-2024-140"],"award-info":[{"award-number":["TU-DSPP-2024-140"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>Clostridium histolyticum is a Gram-positive anaerobic bacterium belonging to the Clostridium genus. It produces collagenase, an enzyme involved in breaking down collagen which is a key component of connective tissues. However, antimicrobial resistance (AMR) poses a great challenge in combating infections caused by this bacteria. The lengthy nature of traditional drug development techniques has resulted in a shift to computer-aided drug design and other modern drug discovery approaches. The above method offers a cost-effective means for gathering comprehensive information about how ligands interact with their target proteins. The objective of this study is to create novel, explicit drugs that specifically inhibit the C. histolyticum collagenase enzyme. Through structure-based virtual screening, a library containing 1830 compounds was screened to identify potential drug candidates against collagenase enzymes. Following that, molecular dynamic (MD) simulation was performed in an aqueous solution to evaluate the behavior of protein and ligand in a dynamic environment while density functional theory (DFT) analysis was executed to predict the molecular properties and structure of lead compounds, and the WaterSwap technique was utilized to obtain insights into the drug\u2013protein interaction with water molecules. Furthermore, principal component analysis (PCA) was performed to reveal conformational changes, salt bridges to express electrostatic interaction and protein stability, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) to assess the pharmacokinetics profile of top compounds and control molecules. Three potent drug candidates were identified MSID000001, MSID000002, MSID000003, and the control with a binding score of \u221210.7 kcal\/mol, \u22129.8 kcal\/mol, \u22129.5 kcal\/mol, and \u22128 kcal\/mol, respectively. Furthermore, Molecular Mechanics Poisson\u2013Boltzmann Surface Area (MMPBSA) analysis of the simulation trajectories revealed energy scores of \u221279.54 kcal\/mol, \u221273.99 kcal\/mol, \u221262.26 kcal\/mol, and \u221270.66 kcal\/mol, correspondingly. The pharmacokinetics properties exhibited were under the acceptable range. The compounds hold the potential to be novel drugs; therefore, further investigation needs to be conducted to find out their anti-collagenase action against C. histolyticum infections and antibiotic resistance.<\/jats:p>","DOI":"10.3390\/computation12080153","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T14:31:07Z","timestamp":1721917867000},"page":"153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification and Dynamics Understanding of Novel Inhibitors of Peptidase Domain of Collagenase G from Clostridium histolyticum"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-6015","authenticated-orcid":false,"given":"Farah","family":"Anjum","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"given":"Ali","family":"Hazazi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, P.O Box 3643, Riyadh 11481, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia"}]},{"given":"Fouzeyyah Ali","family":"Alsaeedi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"given":"Maha","family":"Bakhuraysah","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"given":"Alaa","family":"Shafie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"given":"Norah Ali","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, College of Medicine, King Saud University (KSU), Riyadh 11481, Saudi Arabia"},{"name":"University Family Medicine Center, King Saud University Medical City, King Saud University (KSU), Riyadh 11481, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6127-6508","authenticated-orcid":false,"given":"Nahed","family":"Hawsawi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4579-2921","authenticated-orcid":false,"given":"Amal Adnan","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, Faculty of Dentistry, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2841-5438","authenticated-orcid":false,"given":"Hamsa Jameel","family":"Banjer","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-9850","authenticated-orcid":false,"given":"Afaf","family":"Alharthi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]},{"given":"Maryam Ishrat","family":"Niaz","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences for Nursing, Nursing College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12933","DOI":"10.1021\/acs.jmedchem.2c00785","article-title":"Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases","volume":"65","author":"Alhayek","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Muteeb, G., Rehman, M.T., Shahwan, M., and Aatif, M. (2023). Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review. 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