The accessible surface area (ASA) is the surface area

Surface area

Surface area is the measure of how much exposed area a solid object has, expressed in square units. Mathematical description of the surface area is considerably more involved than the definition of arc length of a curve. For polyhedra the surface area is the sum of the areas of its faces...

 of a biomolecule

Biomolecule

A biomolecule is any molecule that is produced by a living organism, including large polymeric molecules such as proteins, polysaccharides, lipids, and nucleic acids as well as small molecules such as primary metabolites, secondary metabolites, and natural products...

 that is accessible to a solvent

Solvent

A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...

. The ASA is usually quoted in square ångstrom

Ångström

The angstrom or ångström, is a unit of length equal to 1/10,000,000,000 of a meter . Its symbol is the Swedish letter Å....

 (a standard unit

Units of measurement

A unit of measurement is a definite magnitude of a physical quantity, defined and adopted by convention and/or by law, that is used as a standard for measurement of the same physical quantity. Any other value of the physical quantity can be expressed as a simple multiple of the unit of...

 of measurement

Measurement

Measurement is the process or the result of determining the ratio of a physical quantity, such as a length, time, temperature etc., to a unit of measurement, such as the metre, second or degree Celsius...

 in molecular biology

Molecular biology

Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

). ASA was first described by Lee & Richards in 1971 and is sometimes called the Lee-Richards molecular surface. ASA is typically calculated using the 'rolling ball' algorithm developed by Shrake & Rupley in 1973. This algorithm uses a sphere (of solvent) of a particular radius

Radius

In classical geometry, a radius of a circle or sphere is any line segment from its center to its perimeter. By extension, the radius of a circle or sphere is the length of any such segment, which is half the diameter. If the object does not have an obvious center, the term may refer to its...

 to 'probe' the surface of the molecule

Molecule

A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

.

Shrake-Rupley algorithm

The Shrake-Rupley algorithm is a numerical method that draws a mesh of points equidistant from each atom of the molecule and uses the number of these points that are solvent accessible to determine the surface area. The points are drawn at a water molecule's estimated radius beyond the van der Waals radius, which is effectively similar to ‘rolling a ball’ along the surface. All points are checked against the surface of neighboring atoms to determine whether they are buried or accessible. The number of points accessible is multiplied by the portion of surface area each point represents to calculate the ASA. The choice of the 'probe radius' does have an effect on the observed surface area, as using a smaller probe radius detects more surface details and therefore reports a larger surface. A typical value is 1.4Å, which approximates the radius of a water molecule. Another factor that affects the results is the definition of the VDW radii of the atoms in the molecule under study. For example, the molecule may often lack hydrogen atoms which are implicit in the structure. The hydrogen atoms may be implicitly included in the atomic radii of the 'heavy' atoms, with a measure called the 'group radii'. In addition, the number of points created on the van der Waals surface of each atom determines another aspect of discretization

Discretization

In mathematics, discretization concerns the process of transferring continuous models and equations into discrete counterparts. This process is usually carried out as a first step toward making them suitable for numerical evaluation and implementation on digital computers...

, where more points provide an increased level of detail.

LCPO method

The LCPO method uses a linear approximation

Linear approximation

In mathematics, a linear approximation is an approximation of a general function using a linear function . They are widely used in the method of finite differences to produce first order methods for solving or approximating solutions to equations.-Definition:Given a twice continuously...

 of the two-body problem

Two-body problem

In classical mechanics, the two-body problem is to determine the motion of two point particles that interact only with each other. Common examples include a satellite orbiting a planet, a planet orbiting a star, two stars orbiting each other , and a classical electron orbiting an atomic nucleus In...

 for a quicker analytical calculation of ASA. The approximations used in LCPO result in an error in the range of 1-3 Ų.

Applications

Accessible surface area is often used when calculating the transfer free energy required to move a biomolecule from aqueous solvent to a non-polar solvent such as a lipid environment. The LCPO method is also used when calculating implicit solvent

Implicit solvation

Implicit solvation is a method of representing solvent as a continuous medium instead of individual “explicit” solvent molecules most often used in molecular dynamics simulations and in other applications of molecular mechanics...

 effects in the molecular dynamics software package AMBER

AMBER

AMBER is a family of force fields for molecular dynamics of biomolecules originally developed by the late Peter Kollman's group at the University of California, San Francisco. AMBER is also the name for the molecular dynamics software package that simulates these force fields...

.

It is recently suggested that (predicted) accessible surface area can be used to improve prediction of protein secondary structure

Protein structure prediction

Protein structure prediction is the prediction of the three-dimensional structure of a protein from its amino acid sequence — that is, the prediction of its secondary, tertiary, and quaternary structure from its primary structure. Structure prediction is fundamentally different from the inverse...

.

Similar surfaces

The ASA is closely related to the concept of the solvent-excluded surface (also known as the molecular surface or Connolly surface), which is imagined as a cavity in bulk solvent (effectively the inverse of the solvent-accessible surface). It is also calculated in practice via a rolling-ball algorithm developed by Frederic Richards and independently implemented three-dimensionally by Michael Connolly in 1983 and Tim Richmond in 1984. Connolly spent several more years perfecting the method.

External links

• Network Science, Part 5: Solvent-Accessible Surfaces
• AREAIMOL is a command line tool in the CCP4 Program Suite for calculating ASA.
• NACCESS solvent accessible area calculations.
• Surface Racer Oleg Tsodikov's Surface Racer program. Solvent accessible and molecular surface area and average curvature calculation. Free for academic use.
• ASA.py — a Python
  Python (programming language)
  Python is a general-purpose, high-level programming language whose design philosophy emphasizes code readability. Python claims to "[combine] remarkable power with very clear syntax", and its standard library is large and comprehensive...
  
  -based implementation of the Shrake-Rupley algorithm.
• NetSurfP — Secondary Structure and Surface Accessibility. Free for academic use.
• Michel Sanner's Molecular Surface – the fastest program to calculate the excluded surface.
• pov4grasp render molecular surfaces.
• Molecular Surface Package — Michael Connolly's program.
• Volume Voxelator — A web-based tool to generate excluded surfaces.
• VADAR (Volume, Area, Dihedral Angle Reporter) — A web-based tool for analyzing and assessing peptide and protein structures from their PDB coordinate data.
• ASV freeware Analytical calculation of the volume and surface of the union of n spheres (Monte-Carlo calculation also provided).