Computational insights into binding affinity of membrane protein-protein complexes and mutational effects
Confirmed Presenter: Fathima Ridha Karuvanthodikayil, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
Room: Small Theatre
Format: In Person
Moderator(s): Tsuyoshi Shirai
Authors List: Show
- Fathima Ridha Karuvanthodikayil, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
- M. Michael Gromiha, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
Presentation Overview: Show
Membrane protein (MP) complexes play vital cellular functions which are mainly dictated by their binding affinity. Due to their intricate structure, however, binding affinity of MPs is less explored compared to globular proteins. Mutations in these complexes affect their binding affinity, as well as impair critical functions, and may lead to diseases. Despite increase in experimental affinity data in literature, they are dispersed, necessitating their compilation into a comprehensive database for further analysis. Hence, we developed the first and specific database, MPAD (https://web.iitm.ac.in/bioinfo2/mpad), which contains ~5400 experimental binding affinity data of MP complexes and their mutants along with sequence, structure, functional information, membrane-specific features, experimental conditions, and literature information. Next, we developed MPA-Pred (https://web.iitm.ac.in/bioinfo2/MPA-Pred/), the first ML-based method for predicting the affinity of novel MP complexes, which predicts with a correlation of 0.83 and a MAE of 0.88 kcal/mol in jackknife test. Further, we also developed MPA-MutPred, a novel method specific for predicting the binding affinity change upon mutation of MP complexes using an innovative strategy. Our method showed a correlation of 0.75 and MAE of 0.73 kcal/mol using jack-knife test, indicating the reliability. Thus, these resources help enhance understanding of MPs, aiding drug design and enabling further diverse analyses.