Surface exposed residues

Introduction

Electron (or hole) transfer often proceeds from/to surface residues to/from an acceptor/donor inside the protein. Therefore, identification of surface-exposed residues is a key step for prediction of relevant electron/hole transfer pathways. Users can select one of two parameters to classify residues as buried/exposed: residue depth and relative solvent accessibility. In the graph images, buried residues will appear as ovals, while exposed residues will appear as rectangles.

Residue depth

Residue depth is a measure of solvent exposure that describes the extent to which a residue is buried within the protein structure. The parameter was first introduced by Chakravarty [Chakravarty1999] and coworkers, and is computed in PyeMap using the freely available program MSMS. MSMS computes a solvent-excluded surface by rolling a probe sphere along the surface of the protein, which is represented as atomic spheres. The boundary of the volume reachable by the probe is taken to be the solvent-excluded surface. The residue depth for each residue is calculated as the average distance of its respective atoms from the solvent-excluded surface [Sanner1996]. In PyeMap, the threshold for classifying residues as buried/exposed is:

\[\mathbf{RD \leq}~\mathbf{3.03Å}\]

which is the threshold proposed by Tan and coworkers [Tan2009]. Residues 3.03 Å and shallower will be classified as exposed in the final graph; those deeper will be classified as buried. This threshold can be customized by passing the the rd_thresh keyword argument to process().

Please note that MSMS is not available on Mac OS > 10.15, as newer Mac OS do not support 32-bit applications.

Relative Solvent Accessibility

Accessible surface area is a measure of solvent exposure, first introduced by Lee and Richards, which describes the surface area of a biomolecule that is accessible to solvent molecules [Lee1971]. To calculate the accessible surface of each atom, a water sphere is rolled along the surface of the protein, making the maximum permitted van der Waals contacts without penetrating neighboring atoms [Shrake1973]. The total accessible surface area for a residue is the sum of the solvent accessible surface areas of its respective atoms. In order to develop a threshold to classify residues as buried or exposed, calculated ASA values need to be normalized based on corresponding reference values for a given residue. This requires precomputed or predefined maximal accessible surface area (MaxASA) for all residues. MaxASA is the maximal possible solvent accessible surface area for a given residue. MaxASA values are obtained from theoretical calculations of Gly-X-Gly tripeptides in water, where X is the residue of interest. From ASA and MaxASA, the relative solvent accessibility (RSA) can be calculated by the formula:

\[RSA=\frac{ASA}{Max ASA}\]

Several scales for MaxASA have been published. PyeMap uses the most recent theoretical scale from Tien and coworkers [Tien2013]. Relative solvent accessibility is calculated using the DSSP program developed by Kabsch and Sander [Sander1983]. In PyeMap, the RSA threshold chosen for exposed residues is:

\[\mathbf{RSA \geq 0.05}\]

as recommended by Tien and coworkers. Residues with RSA greater than equal to 0.05 will be classified as exposed, those with lower RSA values will be classified as buried. This threshold can be customized by passing the the rsa_thresh keyword argument to process().

Source

pyemap.process_data.calculate_residue_depth(...)	Returns a list of surface exposed residues as determined by residue depth.
pyemap.process_data.calculate_rsa(filename, ...)	Returns a list of surface exposed residues as determined by relative solvent accessibility.