{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:31:20Z","timestamp":1780324280136,"version":"3.54.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"DBT, India","award":["BT\/PR40237\/BTIS\/137\/79\/2023"],"award-info":[{"award-number":["BT\/PR40237\/BTIS\/137\/79\/2023"]}]},{"DOI":"10.13039\/501100004541","name":"Ministry of Education, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mutations in the interface of membrane protein (MP) complexes are key contributors to a broad spectrum of human diseases, primarily due to changes in their binding affinities. While various methods exist for predicting the mutation-induced changes in binding affinity (\u0394\u0394G) in protein\u2013protein complexes, none are specific to MP complexes. This study proposes a novel strategy for \u0394\u0394G prediction in MP complexes, which combines linear and nonlinear models, to obtain a more robust model with improved prediction accuracy. We used multiple linear regression to extract informative features that influence the binding affinity in MP complexes, which included changes in the stability of the complex, conservation score, electrostatic interaction, relatively accessible surface area, and interface contacts. Further, using gradient boosting regressor on the selected features, we developed MPA-MutPred, a novel method specific for predicting the \u0394\u0394G of membrane protein\u2013protein complexes, and it is freely accessible at https:\/\/web.iitm.ac.in\/bioinfo2\/MPA-MutPred\/. Our method achieved a correlation of 0.75 and a mean absolute error (MAE) of 0.73\u00a0kcal\/mol in the jack-knife test conducted on a dataset of 770 mutants. We further validated the method using a blind test set of 86 mutations, obtaining a correlation of 0.85 and an MAE of 0.77\u00a0kcal\/mol. We anticipate that this method can be used for large-scale studies to understand the influence of binding affinity change on disease-causing mutations in MP complexes, thereby aiding in the understanding of disease mechanisms and the identification of potential therapeutic targets.<\/jats:p>","DOI":"10.1093\/bib\/bbae598","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T23:23:36Z","timestamp":1731799416000},"source":"Crossref","is-referenced-by-count":6,"title":["MPA-MutPred: a novel strategy for accurately predicting the binding affinity change upon mutation in membrane protein complexes"],"prefix":"10.1093","volume":"25","author":[{"given":"Fathima","family":"Ridha","sequence":"first","affiliation":[{"name":"Department of Biotechnology , Bhupat and Jyoti Mehta School of Biosciences, , Chennai 600036 ,","place":["India"]},{"name":"Indian Institute of Technology Madras , Bhupat and Jyoti Mehta School of Biosciences, , Chennai 600036 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