AREAIMOL (CCP4: Supported Program)
NAMEareaimol - Analyse solvent accessible areas
SYNOPSISareaimol XYZIN foo_in.pdb [XYZIN2 foo2_in.pdb] [XYZOUT foo_out.pdb]
[Keyworded input] Lee and Richards (1971)) as the locus of the centre of a probe sphere (representing a solvent molecule) as it rolls over the Van der Waals surface of the protein. AREAIMOL calculates the solvent accessible surface area by generating surface points on an extended sphere about each atom (at a distance from the atom centre equal to the sum of the atom and probe radii), and eliminating those that lie within equivalent spheres associated with neighbouring atoms. This is different from the original Lee and Richards (1971) algorithm, which is implemented in the program SURFACE. Note also, that the solvent accessible surface is distinct from the molecular surface, which is the locus of the inward-facing point of the probe sphere (the sum of the contact and re-entrant surfaces).
AREAIMOL finds the solvent accessible area of atoms in a PDB coordinate file, and summarises the accessible area by residue, by chain and for the whole molecule. It will also attempt to identify isolated areas of surface (which could be cavities either within the molecule, or formed as a result of intermolecular contacts). It is capable of excluding specified residues from the calculations, and of generating symmetry related molecules. It can also be used to compare accessible area and analyse area differences. Accessible areas (or area differences) for individual atoms can be written to a pseudo-PDB output file
This is an extensively revised version of the old AREAIMOL program which now also incorporates the functions of DIFFAREA, RESAREA and WATERAREA. The flexibility of the area calculation has been extended by the addition of new keywords PROBE (sets probe radius), PNTDEN (sets precision of area calculation) and ATOM (allows new atom types to be defined).
The keywords are spilt into three groups:
If the SYMMETRY keyword is omitted when SMODE has been specified as IMOL then the program will generate symmetry related molecules assuming P1 symmetry (essentially, lattice translations only). If SMODE is OFF then the SYMMETRY keyword is optional.
Under DIFFMODE IMOL a second SYMMETRY keyword is neccessary, to specify the symmetry operators required for the second area calculation (see below).
Note that unlike previous versions of the program, it is no longer necessary to manually exclude the identity operation when entering symmetry operations. The identity is implicity assumed. If the identity is the only operation that has been entered (or if P1 symmetry is specified) then a warning may appear, but this can be ignored (unless you are not in P1 symmetry).
TRANSlation keyword. This causes the program to generate additional symmetry-related molecules by applying 125 translations made up from linear combinations of the primitive lattice vectors (+/-2 lattice vectors in each direction). Combining these with the spacegroup operators via the SYMMETRY keyword will generate the crystal lattice.
For SMODE IMOL, NONE turns off the translations [default] and TRANS on its own is sufficient to switch them on.
If both <name> and <no> match those belonging to an atom already in the list then its Van der Waal radius will be changed to <radius>. If only one of either match, then the program ignores that occurance of the ATOM keyword and the radius will remain unchanged.
AREAIMOL assumes a single radius for each element, and only recognises a limited number of different elements. Unknown atom types (i.e. those not in AREAIMOL's internal database) will be asigned the default radius of 1.8 A. The list of recognised atoms is:
Name Atomic no. VdW rad. (A) ----------------------------- C 6 1.80 N 7 1.65 O 8 1.60 MG 12 1.60 S 16 1.85 P 15 1.90 CL 17 1.80 CO 27 1.80The ATOM keyword must appear once for each atom definition. The program can store up to twelve new atom types, in addition to those listed above.
Any number of specified residue names can appear together after a single EXCLUDE, separated by a space (eg EXCLUDE PRO ARG GLY). The EXCLUDE keyword can also be repeated any number of times with one or more specified residue names.
There is a maximum number of excluded residues which is set inside the program (currently 30). If there are more than this limit then extra names will not be recorded. Names entered in lower case will automatically be converted to uppercase. Note also that the program does not check that the entries given are valid residue names, or if any are repeated.
In DIFFMODE COMPARE, the named residues will be excluded from both of the input files before the areas are calculated.
In DIFFMODE COMPARE MATCHUP sets the comparision criteria used when doing comparision of XYZIN and XYZIN2:
Atoms which are not included in the comparision are ignored in the output. MATCHUP is only available for DIFFMODE COMPARE.
Note: High values of <point_density> allow more precise estimates of the accessible surface area, but will take longer to calculate - and if <point_density> is too large then the program may exceed its memory resources and stop. At lower values of <point_density> it is possible that atoms with low surface accessibility may be diagnosed as having no accesible surface area at all.
The probe radius must be greater than zero, up to a limit of 25 A. The default radius is 1.4 A.'PRINTER OUTPUT', the log file will also contain the following information:
NB: The input pdb file must contain CRYST1 cards for the OUTPUT option to function.
The program also outputs the contact area for each residue, chain and for the whole molecule. The contact area is defined as the area on the Van der Waals surface of an atom that can be contacted by a sphere of the given probe radius.
For modes NOHOH and ALL the program analyses the atoms which have been assigned accessible area and tries to determine how many isolated areas of surface there are (i.e. areas of surface which are unnconnected to each other on the original molecule). Multiple isolated surfaces could represent any combination of:
In the case when differences in area are calculated (DIFFMODE other than OFF), an additional analysis is presented of the number of each atom type which have non-zero area differences. This is summarised in a table with the following quantities:
There is also a breakdown of accessible area differences by residue, chain and for the whole molecule.
Additional output can be obtained by specifying the VERBOSE keyword. This causes the program to print out diagnostic information such as recognised atom types and radii and the symmetry matrices derived from the symmetry cards.
There were originally four programs to analyse solvent accessible area (AREAIMOL, RESAREA, WATERAREA and DIFFAREA). This version combines the function of the original set of programs into a single run which is controlled by the DIFFMODE keyword:
In the most basic mode of operation the program performs a single area calculation, obtaining the solvent accessibility of each atom under consideration. These individual areas are then used to obtain an analysis of the total accessible area for each residue, chain and for the whole molecule.
The MODE keyword can be used to exclude certain types of residue (e.g. waters) from the calculation. The effect of intermolecular contacts (which will reduce the accessible area) can be included using the SMODE keyword (which generates symmetry-related copies of the original molecule by applying the symmetry operations supplied with the SYMMETRY keyword) and the TRANS keyword (which will apply linear combinations of primitive lattice vectors to the symmetry-related molecules to generate further copies). Combining the primitive lattice vectors with spacegroup symmetry will effectively generate the crystal lattice.
This reproduces the function of the old AREAIMOL program followed by either WATERAREA or RESAREA as appropriate.
Two area calculations are performed, one for each set of supplied symmetry operations (see SYMMETRY and TRANS keywords - if only one set of operators is supplied then the second set is assumed to consist of the identity). The difference in accessible area on each atom is then calculated and the overall area differences analysed.
The SMODE keyword has no function under the DIFFMODE IMOL option, and the SYMMETRY keyword can appear twice: each occurance gives the operators for one calculation of accessible area. Other keywords maintain their function and take effect during both calculations.
Only one set of coordinates is input, and two separate area calculations are carried out (the first treating waters as solvent, i.e. equivalent to MODE HOH, and the second treating them as protein, i.e. equivalent to MODE HOHALL). The area differences are then calculated and output.
The results of the calculations can be interpreted as follows:
The MODE keyword has no function under this option, although the other keywords maintain their function and take effect during both calculations.
Two input coordinate files are required, and two separate area calculations are carried out, one for each set of coordinates. The same MODE and symmetry operators etc (if relevant) are used in each case, so the resulting area differences will depend only on differences between the contents of the files. Area differences are calculated only for those atoms which are common to both files.
E.g. if one file describes a protein bound to a ligand and the other describes the protein alone, then using this mode will calculate the change in surface area of the protein in the presence of the ligand, or more specifically the area obscured by the ligand.
The area calculations also depend critically upon various parameters, such as the probe radius (taken to be 1.4 A for most calculations) and the van der Waals's radii chosen for different atoms. Many programs (including AREAIMOL) choose one radius for all carbons, one radius for all nitrogens, one for all oxygens, whereas others (e.g. SURFACE) are able to differentiate between different carbons (aliphatic, aromatic etc.), different nitrogens and so on.
SURFACE assigns the Van der Waal's radius for a given atom according to both the element and also the residue in which it appears, and thus may lead to differences in estimates of the accessible area.
Note that SURFACE calculates both the accessible area and the contact area, but does not include options for accounting for intermolecular contacts.
Unix examples script found in $CEXAM/unix/runnable/
AUTHOROriginator: Peter Brick, Imperial College
Substantial modifications/additional features: Peter Briggs, CCP4
SEE ALSOsurface, contact