MOLE 2.0: advanced approach for analysis of biomacromolecular channels

Abstract

BackgroundChannels and pores in biomacromolecules (proteins, nucleic acids and their complexes) play significant biological roles, e.g., in molecular recognition and enzyme substrate specificity.ResultsWe present an advanced software tool entitled MOLE 2.0, which has been designed to analyze molecular channels and pores. Benchmark tests against other available software tools showed that MOLE 2.0 is by comparison quicker, more robust and more versatile. As a new feature, MOLE 2.0 estimates physicochemical properties of the identified channels, i.e., hydropathy, hydrophobicity, polarity, charge, and mutability. We also assessed the variability in physicochemical properties of eighty X-ray structures of two members of the cytochrome P450 superfamily.ConclusionEstimated physicochemical properties of the identified channels in the selected biomacromolecules corresponded well with the known functions of the respective channels. Thus, the predicted physicochemical properties may provide useful information about the potential functions of identified channels. The MOLE 2.0 software is available at http://mole.chemi.muni.cz.

Purinergic P2X receptors: Structural models and analysis of ligand-target interaction

“…The comparative analysis among these receptors was extended considering a set of chemicalephysical parameters of the cavity residues. For this step, we followed a protocol analogue to the software Mole [61] based on the calculation of the average values based on different parameters for each considered receptor cavity. Our analysis was hence based on the employment of a set of polarity/hydrophobicity parameters [62e67] calculated for each cavity residue (again, we analysed rP2X1, rP2X3, and rP2X7) and then used to obtain the average values to be compared.…”

Functional importance of a peripheral pocket in mammalian cytochrome P450 2B enzymes

“…All protein model figures were created using MacPyMOL [32]. Channel/cavity analysis was performed using the Graphical User Interface for the Mole 2.0 program on Windows [33]. …”

Conversion of Anthranilate Synthase into Isochorismate Synthase: Implications for the Evolution of Chorismate‐Utilizing Enzymes

“…[4,5] To identify the residues of stTrpE that are involved in this channeling and that may therefore come into contact with the ammonia nucleophile,w ea pplied MOLE 2.0, ap rogram for analyzing macromolecular channels. [6] We identified a3 0-long channel connecting the active sites in stAS (Figure 2a). This channel is similar to the channel observed in the crystal structure of the homologous aminodeoxyisochorismate (ADIC) synthase PhzE.…”