***************************** * Accessible Surface Area * * (ASA) * * Help Screen * ***************************** Accessible surface area (ASA) for each residue is presented under the RES ASA (residue ASA) and FRAC ASA (fractional ASA) headers. The value under the RES ASA column corresponds to the accessible surface area measured in square angstroms. The value under the FRAC ASA column corresponds to the fractional accessible surface area. Accessible surface area is the exposed surface area of the protein (or residue) that a water molecule could access or touch. Exterior or hydrophilic residues typically have a large fraction of ASA, while interior or hydrophobic residues have a small fraction of ASA. Accessible surface area can be reported in square angstroms or as a fractional ASA (ranging from 0.00 to 1.00). The fractional ASA is determined by dividing the observed ASA for a given residue by the calculated ASA for that residue in a Gly-Xaa-Gly tripeptide. VADAR reports ASA values both for the whole residue and for side chains. ASA values are also calculated for polar (N, O, S) atoms, charged atoms (N, O) and for non-polar atoms (C) to permit the calculation of polar, charged and non-polar surface area. These ASA values can be quite useful in structure assessment and thermodynamic calculations. ASA is highly dependent on the choice of atomic or Van der Waals radii. Different authors and sources use different radii and VADAR provides several choices. The Shrake & Rupley numbers (1973) are used as the default. References to Algorithms, Parameters and Programs Used Lee B, Richards FM. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379-400. Richards FM. Areas, volumes, packing and protein structure. Annu Rev Biophys Bioeng. 1977;6:151-176. Eisenberg D, McLachlan AD. Solvation energy in protein folding and binding. Nature. 1986 Jan 16-22;319(6050):199-203. Shrake A, Rupley JA. Environment and exposure to solvent of protein atoms. Lysozyme and insulin. J Mol Biol. 1973 Sep 15;79(2):351-371. Algorithm Details Accessible Surface Area is given in the RES. ASA column in the Main Chain panel, and the SIDE SURF(ASA) column in the Side Chain panel. Accessible Surface Area is defined as the area (measured in square angstroms) of the molecular surface which is contact with solvent. It may also be described as the area over which the centre of a molecule of radius 1.4 angstroms can move while maintaining unobstructed contact with the van der Waals surface of the molecule. The concept of accessible surface area provides a quantitative definition of the exterior and interior of proteins and other macromolecules. ******************* The fractional surface ASA is calcualted by comparing the accessible surface area against a table listing average areas. The residue areas (as well as the atomic areas and side chain areas) were calculated from a peptide created using BIOSYM software with the sequence Gly-Xaa-Gly in the extended (phi=180, psi=-180) position. Each of the twenty amino acids was substituted in the Xaa postion. The area of for each atom in each residue was calculated using ANAREA using atomic radii and/or van der Waals radii from 1) Shrake, 2) Richards 3) some other fellows. These atomic areas and residue areas will be slightly different than those published by Shrake, Richards etc. b because these earlier authors used approximate algorithms. The areas calculated with ANAREA are exact (calculated analytically). The values for the average areas vary depending on the vanderwaals radius chosen in the Main Chain Info section of the parameter file. The tables may be found in the lib directory under tables/area* This is calculated for both the side chain and main chain ASA. ******************* ****************************** * Van der Waals Surface Area * * Help Screen * ****************************** Van der Waals surface area is the actual exposed or visible area of a molecule assuming the atomic surface is defined by the van der Waals radius of each component atom in the molecule. It may also be described as the area over which the centre of an infinitely small point (of radius 0.0 angstroms) can move while maintaining unobstructed contact with the van der Waals surface. The van der Waals surface area is sometimes known as the atomic or molecular surface area. It is nearly equal to the sum of the "contact" and "reentrant" surface areas described by Richards (1977). Note that the van der Waals surface area is always smaller than the ASA and that it is measured in square angstroms. ******************* The main chain info panel gives the total ASA for each residue. The side chain info panel gives only the total ASA for the side chain (everything except the N, C, and O). In addition, the file OUTPUT.area.atom (where OUTPUT is the name of the output file) contains the ASA broken down by individual atom. The file OUTPUT.area.atom is optional and can be turned off in the vadar.parms file (see the help page on vadar.parms). ******************* *** Stats Section on ASA *** Total ASA = Total accessible surface area of the folded protein ASA of backbone = Total accessible surface area of backbone atoms (N,C & O) ASA of sidechains = Total accessible surface area of side chain atoms ASA of C = Total ASA of all carbon atoms in the protein ASA of N = Total ASA of all uncharged nitrogen atoms ASA of N+ = Total ASA of all charged nitrogen atoms ASA of O = Total ASA of all uncharged oxygen atoms ASA of O- = Total ASA of all charged oxygen atoms ASA of S = Total ASA of all sulfur atoms Mean residue ASA = Total ASA divided by the number of residues in the protein Mean frac ASA = Average fractional accessible surface area of each residue in the protein. Fractional ASA's are determined by the measured residue ASA divided by the residue- specific ASA's in the extended state. These vary according the van der Waals radii chosen. % side ASA hydrophobic = the percentage of total side ASA of hydrophobic residues (ALA, VAL, LEU, ILE, PRO, MET, PHE, TRP) to the total side ASA. For all ASA calculations: If the first atom in the input file is an N, then both that N and the last O will be considered charged. For the following discussion, these definitions are used: ASA of C (CASA) = sum of all ASA's for C, CA, CB, CG's, CD's, CE's, CH's, CZ's ASA of N (NASA) = sum of all ASA's for N, ND2, NE, NE1, NH1, NE2 ASA of N+ (NPASA) = sum of all ASA's for NZ, NH2, ND1 ASA of O (OASA) = sum of all ASA's for O, OD1, OE1, OG, OG1, OH (- last O) ASA of O- (OMASA) = sum of all ASA's for OD2, OE2, as well as any OXT atoms (+ last O) ASA of S (SASA) = sum of all ASA's for SG, SD (TASA) = total ASA's And for SHRAKE only these definitions are used: shrake_polar = ASN: CG + GLN: CD - GLU: OE1 - ASP: OD1 - HIS: ND1, HE2 - ARG: NE, NH1 shrake_charged = GLU: OE1, OE2, CD + ASP: CG, OD1, OD2 + HIS: ND1, CE1, NE2 + LYS: NZ + ARG: NE, CZ, NH1, NH2 + ALL: OXT (for the nonpolar definitions, the values that overlap with the total ASA's from above are compensated for in the following SHRAKE definitions); Exposed nonpolar ASA = Total nonpolar accessible surface area. This value has different definitions for different authors and/or choices of van der Waals radii 1) Eisenberg = casa + sasa 2) Chothia = casa 3) Shrake = tasa - charged - polar Exposed polar ASA = Total polar accessible surface area. This value also has different definitions for different authors and/ or choices of van der Waals radii 1) Eisenberg = nasa + oasa - firstN - lastO 2) Chothia = nasa + oasa + sasa - firstN - lastO 3) Shrake = shrake_polar + nasa + oasa + sasa - firstN - lastO Exposed charged ASA = Total charged accessible surface area. This value has different definitions for different authors and/ or choices of van der Waals radii 1) Eisenberg = npasa + omasa + firstN + lastO 2) Chothia = npasa + omasa + firstN + lastO 3) Shrake = shrake_charged + firstN + lastO Fraction nonpolar ASA = Total nonpolar accessible surface area divided by the total accessible surface area Fraction polar ASA = Total polar accessible surface area divided by the total accessible surface area Fraction charged ASA = Total charged accessible surface area divided by the total accessible surface area ******************* *** Expected Values for Stats *** Expected total ASA = Expected total accssible surface area of the folded protein based on its molecular weight (ASA=6.3*MW**.73) Exposed nonpolar ASA = TASA * 0.55 Exposed polar ASA = TASA * 0.30 Exposed charged ASA = TASA * 0.15 Fraction nonpolar ASA \ Fraction polar ASA > value come from where? Fraction charged ASA / *******************