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State\u2010of\u2010art techniques are mostly directed toward finding better targets extracted from the available proteome data. In light of recent computational advancements, we ascertain and validate one such target, adenylosuccinate lyase (<jats:styled-content style=\"fixed-case\">ADSL<\/jats:styled-content>) by implementation of in\u2010silico methods which led to the identification of critical amino acid residues that affects its functional attributes. Our target selection was based on comprehensive topological analysis of a knowledge\u2010based protein\u2013protein interaction network. Subsequently, mutations were incorporated and the dynamic behavior of mutated and native proteins was traced using <jats:styled-content style=\"fixed-case\">MD<\/jats:styled-content> simulations for a total time span of 600\u00a0ns. Comparative analysis of the native and mutated structures exhibited perceptible changes in the ligand\u2010bound catalytic region with respect to time. The unfavorable changes in the orientations of specific catalytic residues, His118 and His196, induced by generated mutations reduce the enzyme specificity. In summary, this integrative approach is able to select a target against pathogen, identify crucial residues, and challenge its functionality through the selected mutations.<\/jats:p>","DOI":"10.1111\/cbdd.13502","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T08:40:49Z","timestamp":1553071249000},"page":"1050-1060","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["An integrative approach using systems biology, mutational analysis with molecular dynamics simulation to challenge the functionality of a target protein"],"prefix":"10.1111","volume":"93","author":[{"given":"Nikita","family":"Bora","sequence":"first","affiliation":[{"name":"Computational Biophysics Laboratory Department of Molecular Biology and Biotechnology Tezpur University  Tezpur Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-2468","authenticated-orcid":false,"given":"Anupam","family":"Nath Jha","sequence":"additional","affiliation":[{"name":"Computational Biophysics Laboratory Department of Molecular Biology and Biotechnology Tezpur University  Tezpur Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh131"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12730"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003440"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1977.tb11885.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.431486"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2013.06.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2012.05.005"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2551-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077011"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi001488j"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi011998t"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2008.11.021"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-77570-8_12"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12639-010-0006-3"},{"key":"e_1_2_7_16_1","unstructured":"Chen S.\u2010H. 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