NanoShaperWeb

A powerful tool for analyzing molecular surfaces and predicting functional sites in protein structures

In structural biology and biophysical modeling, analyzing molecular surfaces and predicting functional sites in protein structures are crucial tasks. Evaluating molecular properties such as volume, surface area, and protein cavities is essential for understanding protein function and contributing to structural drug design.

Core Functionality

NanoShaper is designed to measure molecular properties, construct a Finite Divergence grid for solving PDE, and compute protein pockets. The algorithm works by triangulating the molecular surface using ray-casting to inspect the surface's inner regions in a grid-based space. This process generates an in/out map, allowing for cavity identification, volume estimation, and optional cavity filling.

Volume Estimation

The volume estimation is achieved through a triple ray-casting process, where rays are cast from the x, y, and z axes of the cube containing the molecule. The three resulting volume measurements are averaged for a highly accurate estimate.

Surface Calculation

For molecular surface area calculation, NanoShaper implements a parallel Marching Cubes algorithm. This algorithm triangulates the surface and ensures precise surface area measurements. When voids are removed, the triangulation reflects this by producing a consistent surface representation without cavities.

Surface Types

Connolly-Richards

Classical molecular surface representation

Skin Surface

Alternative smooth molecular surface

Blobby Surface

Gaussian-based representation

Pocket Detection

The identification of internal cavities and pockets uses an intuitive volumetric difference approach, using two probe radii to define regions between solvent-excluded surfaces (SESs).

Probe Sizes

  • Large probe with radius R (default: 3.0 Å)
  • Smaller probe with radius r (default: 1.4 Å)

Effects

  • Higher R value identifies shallow pockets
  • Higher r value smooths inner surface gaps

Technical Details

Implementation

NanoShaper is written in portable and extensible C++, making it adaptable for various applications. Users can analyze PDB files, import MSMS files, and generate molecular surfaces such as skin, blobby, and SES surfaces.

Surface Area Calculation

The surface area calculation is performed using a parallel Marching Cubes algorithm. When voids are removed, the triangulation reflects this by producing a consistent surface representation without cavities.

Volume Estimation Process

The volume estimation process involves a sophisticated triple ray-casting approach:

  • Rays are cast from all the three coordinated planes (xy, xz, yz)
  • Each group of rays cast by a plane provides an independent volume estimation
  • The three measurements are averaged for maximum accuracy

References

  1. Decherchi, Sergio, and Walter Rocchia. "A general and Robust Ray-Casting-Based Algorithm for Triangulating Surfaces at the Nanoscale." Plos One 8, no. 4 (2013): 1-15. https://doi.org/10.1371/journal.pone.0059744.
  2. Krasowski, Agata, Daniel Muthas, Aurijit Sarkar, Stefan Schmitt, and Ruth Brenk. "DrugPred: a structure-based approach to predict protein druggability developed using an extensive nonredundant data set." Journal of chemical information and modeling 51, no. 11 (2011): 2829-2842.
  3. Nicholas Rego, David Koes, 3Dmol.js: molecular visualization with WebGL, Bioinformatics, Volume 31, Issue 8, April 2015, Pages 1322–1324, https://doi.org/10.1093/bioinformatics/btu829.

Cite NanoShaperWeb

If you use NanoShaperWeb in your research, please cite:

BibTeX Format

Download
@article{abate2025nanoshaperweb,
  author={Abate, Carlo and Serra, Eleonora and Rocchia, Walter and Cavalli, Andrea and Decherchi, Sergio},
  title={NanoShaperWeb: Molecular Surface and Pocket Detection Made Visual},
  journal={Journal of Chemical Information and Modeling},
  year={2025},
  month={Jun},
  day={30},
  publisher={American Chemical Society},
  issn={1549-9596},
  doi={10.1021/acs.jcim.5c00821},
  url={https://doi.org/10.1021/acs.jcim.5c00821}
}

ACM Format

Download
Carlo Abate, Eleonora Serra, Walter Rocchia, Andrea Cavalli, and Sergio Decherchi. 2025. NanoShaperWeb: Molecular Surface and Pocket Detection Made Visual. Journal of Chemical Information and Modeling (2025). https://doi.org/10.1021/acs.jcim.5c00821

Contact

For questions and support, please contact:

hpc_servicedesk@iit.it