{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T10:22:34Z","timestamp":1792491754126,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Understanding protein stability is critical for the application of enzymes in biotechnological processes. The structural basis for the stability of thermally adapted chitinases has not yet been examined. In this study, the amino acid sequences and X-ray structures of psychrophilic, mesophilic, and hyperthermophilic chitinases were analyzed using computational and molecular dynamics (MD) simulation methods. From the findings, the key features associated with higher stability in mesophilic and thermophilic chitinases were fewer and\/or shorter loops, oligomerization, and less flexible surface regions. No consistent trends were observed between stability and amino acid composition, structural features, or electrostatic interactions. Instead, unique elements affecting stability were identified in different chitinases. Notably, hyperthermostable chitinase had a much shorter surface loop compared to psychrophilic and mesophilic homologs, implying that the extended floppy surface region in cold-adapted and mesophilic chitinases may have acted as a \u201cweak link\u201d from where unfolding was initiated. MD simulations confirmed that the prevalence and flexibility of the loops adjacent to the active site were greater in low-temperature-adapted chitinases and may have led to the occlusion of the active site at higher temperatures compared to their thermostable homologs. Following this, loop \u201chot spots\u201d for stabilizing and destabilizing mutations were also identified. This information is not only useful for the elucidation of the structure\u2013stability relationship, but will be crucial for designing and engineering chitinases to have enhanced thermoactivity and to withstand harsh industrial processing conditions<\/jats:p>","DOI":"10.3390\/molecules26030707","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T09:25:22Z","timestamp":1611912322000},"page":"707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Computational Analysis of Thermal Adaptation in Extremophilic Chitinases: The Achilles\u2019 Heel in Protein Structure and Industrial Utilization"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5142-7555","authenticated-orcid":false,"given":"Dale L.","family":"Ang","sequence":"first","affiliation":[{"name":"Department of Molecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubasher Zahir","family":"Hoque","sequence":"additional","affiliation":[{"name":"Bio-Bio-1 Research Foundation, Sangskriti Bikash Kendra Bhaban, 1\/E\/1 Poribagh, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Abir","family":"Hossain","sequence":"additional","affiliation":[{"name":"Bio-Bio-1 Research Foundation, Sangskriti Bikash Kendra Bhaban, 1\/E\/1 Poribagh, Dhaka 1000, Bangladesh"},{"name":"Department of Biochemistry and Microbiology, North South University, Plot 15, Block B, Bashundhara, Dhaka 1229, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-3177","authenticated-orcid":false,"given":"Gea","family":"Guerriero","sequence":"additional","affiliation":[{"name":"Research and Innovation Department, Luxembourg Institute of Science and Technology, 5, rue Bommel, Z.A.E. Robert Steichen, L-4940 Hautcharage, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Berni","sequence":"additional","affiliation":[{"name":"TERRA Teaching and Research Center, Gembloux Agro-Bio Tech, University of Li\u00e8ge, 5030 Gembloux, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-7817","authenticated-orcid":false,"given":"Jean-Francois","family":"Hausman","sequence":"additional","affiliation":[{"name":"Research and Innovation Department, Luxembourg Institute of Science and Technology, 5, rue Bommel, Z.A.E. Robert Steichen, L-4940 Hautcharage, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleem A","family":"Bokhari","sequence":"additional","affiliation":[{"name":"Biosciences Department, COMSATS University Islamabad, Park Road, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wallace J.","family":"Bridge","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences (BABS), University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khawar Sohail","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences (BABS), University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Funkhouser, J.D., and Aronson, N.N. 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