Conditional Hydrophobic Accessible Surface Area (CHASA)

CHASA is a method to calculate the Conditional Hydrophobic Accessible Surface Area of protein model structures.

CHASA is sensitive to the effects of neighboring polar atom solvation and provides a more appropriate estimation of the hydrophobic solvation free energy in an amphipathic molecule such as a polypeptide than traditional hydrophobic ASA.

The Conditional Accessible Surface Area (CASA) calculates the accessible surface area (ASA) conditional upon prior solvation of the backbone N and O atoms by placing an oxygen atom proximate to these backbone atoms at acceptable hydrogen bond distance and orientation and then including these solvation "waters" in the ASA calculation. CHASA is the hydrophobic component of this CASA.

The number of successfully solvated backbone N and O atoms provides an estimate of the polar solvation free energy; the CHASA provides an estimate of the non-polar solvation free energy. Together these two values may be used to calculate a total solvation free energy for a polypeptide.

A paper in press in Protein Science describes these methods in detail.

This work was done in collaboration with Mihaly Mezei at the Mount Sinai School of Medicine in New York. His website also has software for simulating peptides and proteins in explicit solvent.

CHASA Program

A Python program is available for calculating CHASA and solvation free energy. Note: This program requires that you have Numeric installed in your Python distribution.

Also, the PDB file parser is not robust. It expects a very clean PDB file with no unusual atom types, alternate conformations, etc. If you have trouble with your PDB file try cleaning it up by downloading the C-shell/awk script extract.csh and typing: 

      chmod a+x extract.csh
      extract.csh pdb[xxx].ent
This will create a new file called pdb[xxx].cln with most standard offenses removed.

Dr. Mezei's website also has a useful utility for cleaning up and manipulation of PDB files in preparation for analysis or simulation called Simulaid.

CHASA Web Server

A CHASA server is also available to calculate CHASA solvation free energy.

CHASA Program and Server Output

Output from both the program and the server is in the form of a PDB file with results in the occupancy and B-factor columns and header and TER records.

Example: 

COMPND numintHbd     numSolv    num_nonHbd      total_bb_polar
COMPND     84          147           3              111
.
.
.
ATOM      9  N   THR     2      13.719  19.413  27.573  5.00  0.00
ATOM     10  CA  THR     2      13.088  19.661  26.283  0.00  0.00
ATOM     11  C   THR     2      13.561  18.631  25.300  0.00  0.00
ATOM     12  O   THR     2      14.763  18.432  25.121  3.00  1.57
ATOM     13  CB  THR     2      13.527  20.980  25.667  0.00  7.80
ATOM     14  OG1 THR     2      13.307  22.020  26.627  0.00  5.84
ATOM     15  CG2 THR     2      12.704  21.284  24.409  0.00 16.10
.
.
.
ATOM    149  N   ALA    20       9.346  17.206  29.144  0.00  0.49
ATOM    150  CA  ALA    20       8.985  15.930  29.750  0.00  2.64
ATOM    151  C   ALA    20      10.067  15.607  30.760  0.00  3.52
ATOM    152  O   ALA    20      11.193  16.119  30.686 -1.00  1.77
ATOM    153  CB  ALA    20       8.856  14.815  28.714  0.00  2.39
.
.
.
ATOM    499  O   HOH   120       7.787   1.168  13.283  0.00  0.00
ATOM    500  O   HOH   121       9.368  -0.535   6.166  0.00  0.00
ATOM    501  O   HOH   122      22.918  12.605  15.164  0.00  0.00
ATOM    502  O   HOH   123      16.522  12.543  26.647  0.00  0.00
ATOM    503  O   HOH   124      22.421   8.292  28.255  0.00  0.00
ATOM    504  O   HOH   125      11.087  12.195  10.474  0.00  0.00
TER 1424.592  -52.662

where:

        numintHbd = number of internally hydrogen bonded backbone N and O

        numSolv = number of solvation "waters" (max = 5 per backbone polar group)

        num_nonHbd = number of backbone polar groups not satisfied by hydrogen bonding

        total_bb_polar = number of backbone polar groups in the molecule that should
                         be hydrogen bonded ([2 x Number of residues] -1)

        occupancy column (for N and O only):
            (if > 0.00) = number of solvation "waters" accessible to that atom (max = 5)
            (if = -1.00) = this atom is not hydrogen bond satisfied

        B factor column = CHASA in square angstroms

        TER record:
            (first number) = total CHASA for molecule
            (second number) = solvation free energy for molecule (See below for explanation)

        HOH atoms = solvation "waters" in hydrogen bonding proximity to backbone polar groups
                    (these are the conditional atoms added prior to ASA calculation)
Note: The N-terminal nitrogen is not solvated and thus the CHASA value for some atoms proximate to this atom in cartesian space will be standard hydrophobic ASA not conditional hydrophobic ASA.

Note: The solvation free energy is calculated as follows:

    Total solvation free energy = non-polar + polar solvation free energy, where

      Non-polar solvation free energy = total conditional hydrophobic accessible surface area (CHASA) x 0.03

      Polar solvation free energy = backbone polar atom solvation free energy, where

        Backbone N and O solvation is attempted by placing pseudo water at 5 different postions at appropriate distance and orientation for hydrogen bonding. The number of successfully placed pseudo waters with no steric clash x 0.6 = polar solvation free energy. Backbone oxygens may also be both internally hydrogen bonded AND hydrogen bonded to water. In this case a value of 2.0 is assigned to the solvation free energy of the oxygen.

      Bug reports to Pat Fleming are appreciated.