Publications by authors named "Sagara N S Gurusinghe"
Article Synopsis
- * Current methods to predict the changes in binding energy (ΔΔG) due to mutations are often imprecise, but recent developments in protein language models (PLMs) show promise for better predictions by using both sequence and structural information.
- * The new model, ProBASS, utilizes advanced PLMs to accurately predict the effects of mutations on PPI binding affinity, achieving a high correlation with experimental ΔΔG values and outperforming existing methods, paving the way for advancements in protein engineering and design.
BMC Bioinformatics
April 2024
Article Synopsis
- - Protein-protein interactions (PPIs) involve specific binding surfaces on proteins, where critical features of these surfaces affect the dynamics of interactions and influence protein evolution, including the identification of "hot spots" and "cold spots."
- - The study introduces Cold Spot SCANNER, a user-friendly tool that detects cold spots in PPI interfaces by analyzing structural features like cavities and unfavorable interactions, while also providing visualization options using Py3DMOL.
- - This software is freely accessible without login requirements, aiding in protein engineering research and enhancing understanding of protein evolution, available at a specified Google Colab link.
Article Synopsis
- Proteins interact at binding interfaces where "hot spots" significantly contribute to binding energy, while "cold spots" can be targeted for enhancing affinity through mutations.
- The study identifies cold spots linked to cavities and charge interactions by analyzing a small affinity database and nearly 4000 protein structures, revealing that cold spots are common across various protein-protein interactions (PPIs).
- Findings indicate that cold spots are typically peripheral, more frequent in non-cognate interactions, and prevalent in homo-dimers, with specific amino acids like glycines, glutamates, and arginines often found at these sites, highlighting their role in protein evolution and engineering.
