Protein Functional Surfaces: Global Shape Matching and Local Spatial Alignments of Ligand Binding Sites
Author Information
Author(s): Binkowski T Andrew, Joachimiak Andrzej
Primary Institution: Midwest Center for Structural Genomics and Structural Biology Center, Argonne National Laboratory
Hypothesis
Can surface shape and local physicochemical texture be optimized to evaluate the similarity between protein surfaces?
Conclusion
The study presents a new method for comparing protein functional surfaces, demonstrating its effectiveness in identifying homologous binding sites and predicting functions for proteins of unknown function.
Supporting Evidence
- SurfaceScreen can identify functionally homologous surfaces binding different ligands.
- The method was benchmarked against known protein-ligand complexes.
- Results indicate that surface shape and physicochemical texture are key to predicting protein function.
- SurfaceScreen achieved a retrieval rate of 84.7% for HIV-1 protease-ligand complexes.
Takeaway
This study shows how proteins can have similar shapes and functions even if they look different at the sequence level, helping scientists find new uses for existing drugs.
Methodology
The study introduces SurfaceScreen, a method that combines global shape matching and local spatial alignments to compare protein surfaces.
Limitations
The method does not account for amino acid substitutions during spatial alignments, which may affect the accuracy of surface comparisons.
Statistical Information
P-Value
9.84 × 10^-3
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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