Calculation of accurate interatomic contact surface areas for the quantitative analysis of non-bonded molecular interactions.

Judemir Ribeiro,Francisco Melo,Andreas Schüller,Carlos Ríos-Vera,Alfonso Valencia

doi:10.1093/bioinformatics/btz062

Abstract

SummaryIntra- and intermolecular contact surfaces are routinely calculated for a large array of applications in bioinformatics but are typically approximated from differential solvent accessible surface area calculations and not calculated directly. These approximations do not properly take the effects of neighboring atoms into account and tend to deviate considerably from the true contact surface. We implemented an extension of the original Shrake-Rupley algorithm to accurately estimate interatomic contact surface areas of molecular structures and complexes. Our extended algorithm is able to calculate the contact area of an atom to all nearby atoms by directly calculating overlapping surface patches, taking into account the possible shielding effects of neighboring atoms. Here, we present a versatile software tool and web server for the calculation of contact surface areas, as well as buried surface areas and solvent accessible surface areas (SASA) for different types of biomolecules, such as proteins, nucleic acids and small organic molecules. Detailed results are provided in tab-separated values format for analysis and Protein Databank files for visualization. Direct contact surface area calculation resulted in improved accuracy in a benchmark with a non-redundant set of 245 protein–DNA complexes. SASA-based approximations underestimated protein–DNA contact surfaces on average by 40%. This software tool may be useful for surface-based intra- and intermolecular interaction analyses and scoring function development.Availability and implementationA web server, stand-alone binaries for Linux, MacOS and Windows and C++ source code are freely available from http://schuellerlab.org/dr_sasa/.Supplementary information Supplementary data are available at Bioinformatics online.

Highlights

1.1 Calculation of the solvent accessible surface area of a molecule For the calculation of the solvent accessible surface area or Solvent Accessible Surface Area (SASA), the Shrake and Rupley algorithm was used (Shrake and Rupley, 1973). It consists in generating a spherical cloud of points for each atom, where each point is at a distance equivalent to the van der Waals radius plus the radius of a water molecule (1.4 Å by default) from the atom center
Supports proteins Supports DNA/RNA Supports small molecules Guessing of unknown atom radii Supports MOL2 format Supports per atom contact surface areas (CSA) calculation Supports buried surface area (BSA) interface calculation Supports chain selections Supports per atom detailed output Source code available Offline usage Web server available dr_sasa YYYYYYYYYYYY
We interpreted the results of this section as increased accuracy of dr_sasa due to its ability to calculate CSA directly from surface overlaps

Summary

Methods

1.1 Calculation of the solvent accessible surface area of a molecule For the calculation of the solvent accessible surface area or SASA, the Shrake and Rupley algorithm was used (Shrake and Rupley, 1973). The contact surface area mode of operation (mode 1, command line switch: -m 1) requires the selection of the chains to be considered as separate objects, or if the PDB or Mol file contains different types of biomolecules (protein and nucleic acids, protein and ligands, or any combination of the three) the program will automatically identify the separate objects and calculate their interactions. In this mode the output is presented as two types of matrices. The web server does generate contact map plots by default (Figure S4)

Output files

Feature comparison

Findings

Benchmarks