Protein signatures using electrostatic molecular surfaces in harmonic space

PeerJ. 2013 Oct 22;1:e185. doi: 10.7717/peerj.185. eCollection 2013.


We developed a novel method based on the Fourier analysis of protein molecular surfaces to speed up the analysis of the vast structural data generated in the post-genomic era. This method computes the power spectrum of surfaces of the molecular electrostatic potential, whose three-dimensional coordinates have been either experimentally or theoretically determined. Thus we achieve a reduction of the initial three-dimensional information on the molecular surface to the one-dimensional information on pairs of points at a fixed scale apart. Consequently, the similarity search in our method is computationally less demanding and significantly faster than shape comparison methods. As proof of principle, we applied our method to a training set of viral proteins that are involved in major diseases such as Hepatitis C, Dengue fever, Yellow fever, Bovine viral diarrhea and West Nile fever. The training set contains proteins of four different protein families, as well as a mammalian representative enzyme. We found that the power spectrum successfully assigns a unique signature to each protein included in our training set, thus providing a direct probe of functional similarity among proteins. The results agree with established biological data from conventional structural biochemistry analyses.

Keywords: Drug design; Electrostatic potentials; Harmonic space; Protein similarity search; Structural biology.

Grant support

This study was supported by the European Union (European Social Fund—ESF), received Greek national funds through the Operational Program ‘Education and Lifelong Learning’ of the National Strategic Reference Framework (NSRF)—Research Funding Program: Shales, and the Investing in Knowledge Society through the European Social Fund. CSC is funded by the FCT-Lisbon, Grant no. SFRH/BPD/65993/2009. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.