Protein Molecular Surface Mapped at Different Geometrical Resolutions

Abstract

Many areas of biochemistry and molecular biology, both fundamental and applications-orientated, require an accurate construction, representation and understanding of the protein molecular surface and its interaction with other, usually small, molecules. There are however many situations when the protein molecular surface gets in physical contact with larger objects, either biological, such as membranes, or artificial, such as nanoparticles. The contribution presents a methodology for describing and quantifying the molecular properties of proteins, by geometrical and physico-chemical mapping of the molecular surfaces, with several analytical relationships being proposed for molecular surface properties. The relevance of the molecular surface-derived properties has been demonstrated through the calculation of the statistical strength of the prediction of protein adsorption. It is expected that the extension of this methodology to other phenomena involving proteins near solid surfaces, in particular the protein interaction with nanoparticles, will result in important benefits in the understanding and design of protein-specific solid surfaces.

Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution

“…overall hydrophobicity is the hydrophobicity of the amphiphilic protein (previously [29] denominated as amphiphilicity), calculated as the algebraic sum of the total hydrophobicity and total hydrophilicity of the units exposed on the molecular surface, calculated by either using amino-acid, or atom-based methodologies.…”

“…Indeed, the probing of proteins that exhibit concave shapes, most notably channel proteins, by probes with increasing radii will produce unreliable results, because much of their interior molecular surface will be inaccessible to larger probes. Finally, to ensure a representative comparison between the atomic- and amino acid-based hydrophobicity, the selected set of proteins is identical with the one used in a previous contribution [29] , which reports on the probing of protein molecular surfaces with probes of different sizes.…”

“…The calculations used an in-house program [29] , which is an upgrade of the Connolly’s original software code [23] , [47] , embedded in a Windows interface. The program has been run on a personal computer with a 64-bit operating system, an Intel Core i7-3630QM CPU @2.40 GHz, and an installed memory of 8GB.…”

“…The molecular surfaces have been constructed for all 35 proteins in the dataset ( Table 1 ), for probe radii ranging from 1.4 Å to 20 Å. Beyond probe radii of 20 Å it was found [29] that the change of the properties on the molecular surface is negligible. Consequently the calculations stopped at this threshold.…”

“…Indeed, the representation of the molecular surface, which relies on procedures [21] – [27] that use the protein structure deposited in databases, such as Protein Database, PDB [28] , usually uses a geometrical resolution between 1.4 to 5 Å, which represents the size of the small molecular species the proteins interact with. However, as discussed before [29] , there are many situations that justify the use of larger probes because the protein interacts with larger objects, e.g., membrane lipid rafts [30] , cytoskeleton proteins [31] , amyloid plaques [32] , biomaterials surface [33] , biomedical micro-devices [34] , [35] and chromatographic media [36] . Also, from the methodology point of view, the probing of the molecular surfaces with at different geometrical resolutions, i.e., using different probe radii, can reveal structural features of the proteins, e.g., shielding of the hydrophobic core [29] .…”