Work

KDSAXS: A Tool for Analyzing Binding Equilibria With SAXS Data Using Explicit Models

Year: 2025

Type: article

Abstract: Computational tool for K D estimation Models complex equilibria from SAXS titration data, including oligomerization, ligand and multivalent interactions. Integration with structural data Uses experimental or computational models, including X-ray, NMR, AlphaFold, and molecular dynamics simulations. User-friendly interface Provides an interactive dashboard for SAXS data input, model validation, and analysis of species populations and scattering. Broad accessibility Open-source web tool with customizable models and visualizations, requiring no advanced computational expertise. K D SAXS is a computational tool for estimating dissociation constants (K D ) from small-angle X-ray scattering (SAXS) titration experiments. By combining ensemble analysis with mass-balance equations, K D SAXS effectively models complex equilibria involving multiple species, ranging from simple oligomerization to transient and multivalent interactions, including intrinsically disordered proteins. For each species in equilibrium, the tool supports the integration of theoretical scattering profiles derived from ensemble structural models, X-ray crystallography, NMR, AlphaFold predictions, or molecular dynamics simulations. With its intuitive dashboard interface, K D SAXS enables researchers to input SAXS titration data, validate structural models and interactions, and compute species-specific scattering profiles. Additionally, it determines the relative populations of biomolecular species in equilibrium across user-defined Kᴅ ranges and concentrations. Applications of K D SAXS to systems such as beta-lactoglobulin oligomerization and the PCNA-p15PAF complex highlight its capacity to resolve complex equilibria and deliver accurate K D estimations. As an open-source platform, K D SAXS bridges computational and experimental methodologies, advancing SAXS-based analysis of macromolecular interactions and enhancing insights into dynamic biological systems. K D SAXS is freely accessible as a web server at https://kdsaxs.itqb.unl.pt .

Source: Journal of Molecular Biology

DOI: 10.1016/j.jmb.2025.169103