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Updated: Apr 17, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
The impact of side-chain packing on protein docking refinement
Mohammad Moghadasi1, Hanieh Mirzaei1, Artem Mamonov1
1†Division of Systems Engineering, ‡Center for Information and Systems Engineering, §Department of Biomedical Engineering, ∥Department of Mechanical Engineering, and ⊥Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, United States.
Abstract:
We study the impact of optimizing the side-chain positions in the interface region between two proteins during the process of binding. Mathematically, the problem is similar to side-chain prediction, which has been extensively explored in the process of protein structure prediction. The protein-protein docking application, however, has a number of characteristics that necessitate different algorithmic and implementation choices. In this work, we implement a distributed approximate algorithm that can be implemented on multiprocessor architectures and enables a trade-off between accuracy and running speed. We report computational results on benchmarks of enzyme-inhibitor and other types of complexes, establishing that the side-chain flexibility our algorithm introduces substantially improves the performance of docking protocols. Furthermore, we establish that the inclusion of unbound side-chain conformers in the side-chain positioning problem is critical in these performance improvements. The code is available to the community under open source license.
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