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Recent studies have proposed purine nucleoside phosphorylase from P. falciparum (PfPNP) as a potential target for malaria treatment. In the present study, we designed a virtual library of 400 dipeptides to discover novel anti\u2010malarial peptide inhibitors. A structure\u2010based molecular docking method was employed to virtually screen the designed library against the wild\u2010type structure of PfPNP (PDB: 5ZNC). The best four (Phe\u2010Arg, Arg\u2010His, Trp\u2010Arg and Tyr\u2010Arg) dipeptides, which were then investigated for their binding potential against PfPNP using Molecular Dynamics simulation studies. Parameters such as RMSD, RMSF, Rg, and SASA were analyzed to understand the structural changes, energetics, and overall behavior of PfPNP\u2010dipeptide complexes. The PfPNP demonstrated significant stability upon binding with each of the identified dipeptides with \u0394G of over \u2212168\u2005kcal\/mol. Additionally, DFT and ADME predictions indicated that the electronic structure, energetics, and pharmacokinetic properties of Phe\u2010Arg, Arg\u2010His, Trp\u2010Arg and Tyr\u2010Arg were favourable for drug development. Our comprehensive computational investigation has identified these four dipeptides as promising candidates. These designed and selected dipeptides may further be modified using peptidomimetic and medicinal chemistry tools to develop a novel class of promising antimalarials.<\/jats:p>","DOI":"10.1002\/cbdv.202401668","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T12:58:47Z","timestamp":1727701127000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel Dipeptide Inhibitors of PfPNP: In\u2010Silico Identification of Promising New Antimalarials"],"prefix":"10.1002","volume":"22","author":[{"given":"Kanika","family":"Devi","sequence":"first","affiliation":[{"name":"School of Physical Sciences Jawaharlal Nehru University  New Delhi 110067 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshuman","family":"Chandra","sequence":"additional","affiliation":[{"name":"School of Physical Sciences Jawaharlal Nehru University  New Delhi 110067 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susmita","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Centre for Biodesign Translational Health Science and Technology Institute  Faridabad, Haryana 121001 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-0323","authenticated-orcid":false,"given":"Vijay","family":"Kumar Goel","sequence":"additional","affiliation":[{"name":"School of Physical Sciences Jawaharlal Nehru University  New Delhi 110067 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"crossref","unstructured":"Li J. 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