................ SHORT DOC ............................................. ASV: Analytical calculation of van der Waals surfaces and volumes Reference: M. Petitjean, On the Analytical Calculation of van der Waals Surfaces and Volumes: Some Numerical Aspects, J. Comput. Chem. 1994,15[5],507-523 Author email: petitjean@itodys.jussieu.fr ASV reads the cartesian coordinates of the molecule and the van der Waals radii of the atoms, then performs both Monte-Carlo and analytical calculation of the van der Waals surface and volume. Input data and parameters: ------------------------- INPUT FORMAT: CAS : Reserved for internal purposes HIN : Hyperchem-type files MDL : Cambridge Crystallographic Model files ML2 : SYBYL Mol2 files PDB : Protein Data Bank or Nucleic Acid Data Bank files (only HEADER, ATOM, ENDMDL and END records are recognized) BIO : Biosym (MSI) files ISU : Reserved for internal purposes INPUT MOLEC FILE NAME: name of the input file containing the molecule IMOL: Sequential position number of the molecule in the input file van der Waals radii: SYMBOL=RADIUS , SYMBOL=RADIUS ... When SYMBOL is a valid chemical symbol, all atoms bearing this symbol type get a van der Waals radius equal to RADIUS. When SYMBOL is an number pertaining to [1..N], N being the number of atoms of the molecule, the pointed atom get the assigned RADIUS, dicsarding the rest of the SYMBOL=RADIUS list. Exemple: "H=1.17 , 34=1.5 , C=1.75 , Cl=1.77" means that the atom number 34 in the molecule file get the radius 1.5, discarding if it is a carbon, an hydrogen or anything else. Atoms cited neither by symbol nor by number get a null radius. OUTPUT ATOMIC RADII AND COORD: Enter an integer number n. The n first atomic radii and coordinates are printed. Nothing is printed if n is not positive. NOBST: Number of random points for the Monte-Carlo estimation of surface and volume. No Monte-Carlo is done when a negative or null value is entered. NPERM: Number of additional analytical calculations performed with random rotated and renumbered copies of the molecule. No analytical calculation is done when a negative value is entered. The analytical calculation is done when NPERM=0 is entered. When NPERM>0, NPERM additional analytical calculations are done with random copies. Among the NPERM+1 analytical calculations, the first one is done on the original non rotated non renumbered molecule. EPSTAB: Generate randomly perturbated cartesian coordinates. Independant random 3-tuples (x,y,z) are added to the spatial atomic positions. Each random 3-tuple is uniformly distributed in a sphere with radius equal to EPSTAB and centered on the atomic position. The coordinates are not modified when EPSTAB is negative or null. The EPSTAB parameter applies even when NPERM=0. ILIST: Any positive value indicates than the surface and volume of all sphere overlaps are printed. No overlap list is printed when ILIST is negative or null. CAUTION : activating the ILIST parameter may cause considerable amounts of output for medium or large molecule. Output results: -------------- When NOBST positive: The estimated surface and volume of the union of the van der Waals spheres, the associated standard deviations and the ratio of the standard deviation to the Monte-Carlo estimate. When NPERM is not negative, NPERM+1 analytical calculations are done. For each analytical calculation, the number of overlaps, the surface and volume, and the sphericity index are printed. Remarks: ------- The number of atoms is currently limited to 15000 for each molecule. The source has to be recompiled to read larger molecules. ASV computes the surface and volume of any union or intersection of spheres, discarding whether it is a molecular model or not. The sphericity index is computed as follows: the squared volume is divided by the cube of the surface, and the ratio is multiplied by 36*pi to get the sphericity index pertaining to ]0;1]. The analytical surfaces and volumes are printed with six decimals. The NPERM parameter is useful to detect if some numerical instability appears. When this situation is detected, the EPSTAB parameter can be used to remove them (e.g. try EPSTAB=1.E-6). Using small values of EPSTAB may be also useful to evaluate the numerical impact of the precision of the coordinates upon the surfaces and volumes. The ILIST parameter is useful to compute the surface and volume of the intersections of any number of spheres, rather than their union. The number of random observations (NOBST) should be multiplied by 100 to get a standard deviation of the Monte-Carlo estimate divided by 10. The computing time of the analytical calculation is mainly related to the number of overlaps. This latter can be very high for large molecules, such as proteins. Thus, for QSAR and other poor precision applications involving large molecules, Monte-Carlo estimates should be preferred to analytical calculations. These latter are rather used when a high precision is required, such as computing finite difference approximations of gradients. ....................... END SHORT DOC ................................