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Protein–DNA interactions play an important role in various biological processes such as gene expression, replication, and transcription. Understanding the important features that dictate the binding affinity of protein-DNA complexes and predicting their affinities is important for elucidating their recognition mechanisms. In this work, we have collected the experimental binding free energy (ΔG) for a set of 391 Protein-DNA complexes and derived several structure-based features such as interaction energy, contact potentials, volume and surface area of binding site residues, base step parameters of the DNA and contacts between different types of atoms. Our analysis on relationship between binding affinity and structural features revealed that the important factors mainly depend on the number of DNA strands as well as functional and structural classes of proteins. Specifically, binding site properties such as number of atom contacts between the DNA and protein, volume of protein binding sites and interaction-based features such as interaction energies and contact potentials are important to understand the binding affinity. Further, we developed multiple regression equations for predicting the binding affinity of protein-DNA complexes belonging to different structural and functional classes. Our method showed an average correlation and mean absolute error of 0.78 and 0.98 kcal/mol, respectively, between the experimental and predicted binding affinities on a jack-knife test. We have developed a webserver, PDA-PreD (Protein-DNA Binding affinity predictor), for predicting the affinity of protein-DNA complexes and it is freely available at https://web.iitm.ac.in/bioinfo2/pdapred/
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This content will become publicly available on May 1, 2026
Sparse identification of nonlocal interaction kernels in nonlinear gradient flow equations via partial inversion
We address the inverse problem of identifying nonlocal interaction potentials in nonlinear aggregation–diffusion equations from noisy discrete trajectory data. Our approach involves formulating and solving a regularized variational problem, which requires minimizing a quadratic error functional across a set of hypothesis functions, further augmented by a sparsity-enhancing regularizer. We employ a partial inversion algorithm, akin to the CoSaMP and subspace pursuit algorithms, to solve the basis pursuit problem. A key theoretical contribution is our novel stability estimate for the PDEs, validating the error functional ability in controlling the 2-Wasserstein distance between solutions generated using the true and estimated interaction potentials. Our work also includes an error analysis of estimators caused by discretization and observational errors in practical implementations. We demonstrate the effectiveness of the methods through various 1D and 2D examples showcasing collective behaviors.
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- PAR ID:
- 10625974
- Publisher / Repository:
- World Scientific
- Date Published:
- Journal Name:
- Mathematical Models and Methods in Applied Sciences
- Volume:
- 35
- Issue:
- 05
- ISSN:
- 0218-2025
- Page Range / eLocation ID:
- 1073 to 1131
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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