SAXSDom

SAXSDom assembles multidomain protein structures by integrating small-angle X-ray scattering (SAXS) data to guide domain-domain arrangement when only individual domain templates are available.

Key Features:

• Integration of SAXS Data: Experimental small-angle X-ray scattering (SAXS) profiles are used to constrain and evaluate domain arrangements during assembly.
• Probabilistic Input-Output Hidden Markov Model (IOHMM): Employs an IOHMM to assemble individual domain structures into coherent full-length models.
• Four SAXS-based Scoring Functions: Implements four scoring functions derived from SAXS data to evaluate the compatibility of proposed assemblies with experimental SAXS profiles.
• Domain-template Assembly: Targets cases where structural templates are available for individual domains but not for the entire sequence.
• Benchmarking on Public Datasets: Incorporation of SAXS information improved domain assembly accuracy for 40 out of 46 critical assessment targets and 45 out of 73 ab initio domain assembly targets from two public datasets.

Scientific Applications:

• Complementing Homology Modeling: Improves domain-domain assembly predictions when complete homology templates for full-length proteins are unavailable.
• Functional and Interaction Inference: Provides structural models to aid interpretation of protein function and protein–protein interactions.
• Structure-guided Design: Supports structure-based drug design and molecular engineering by providing improved multidomain models.

Methodology:

Integration of experimental SAXS data with individual-domain structural models; probabilistic domain assembly using an Input-Output Hidden Markov Model (IOHMM); evaluation of assemblies using four SAXS-based scoring functions.