Chemistry Reference
In-Depth Information
available from the Protein Data Bank (PDB) archive (Berman et al.
2000
). In October
8, 2013, this archive contained 94540 structures. Another important data bank in
protein science is Universal Protein Resource (UniProt), a comprehensive resource
for protein sequence and functional information (Jain et al.
2009
).
Within this chapter, a few web-based tools concerning the proteins surface prop-
erties visualization and analysis are reviewed in correlation with their applicability to
the protein-ligand and protein-protein interactions prediction, analysis and/or char-
acterization. There also are illustrative examples presented in a didactic manner in
order to allow to young scientists (students, PhD students) to reproduce the study
and to facilitate the use of described computational tools.
9.2
Proteins Surface Analysis and Comparison
It is well known that interactions between macromolecules are usually determined
by the properties of their surfaces. The surface of a protein is irregular and presents
cavities and channels with different shapes, sizes and chemical properties that are
crucial for many phenomena such as: molecular recognition and binding, diffu-
sion and absorption of small molecules, enzyme catalysis, interactions with other
macromolecules, etc.
There is not a generally accepted definition for protein surface but a few ap-
proaches are used to define it (Gerstein et al.
2001
). The simplest is the van der
Waals surface (VDWS), defined as the sum of exposed areas of the constituent atoms
modeled as spheres with radii known from their van der Waals properties. Another
approach, using the term of probe-sphere rolling around the surface, concerns the
contact surface (CS). It is defined as the surface containing all contact points of the
molecule and the probe particle. When this particle touches more than one atom we
obtain the reentrant surface (RS). The sum between the contact and reentrant surfaces
defines the molecular surface (MS
RS). The accessible solvent area (ASA) is
defined as the surface generated by the centers of the probe particle rolling along the
protein. When using the probe-sphere approach, the protein surfaces computation
greatly depends on the value chosen for the probe-sphere radius that is frequently,
but not always, set at a value considered to represent a water molecule, 1.4 Å, and
there is not an agreement on what the proper radius should be. Table
9.1
shows the
solvent accessible surface area computed for bovine recoverin (a calcium binding
protein) for different probe-sphere radii using GETAREA software (Fraczkiewicz
and Brown
1998
). GETAREA is a web service provided by the University of Texas
Medical Branch (http://curie.utmb.edu/getarea.html). The input file for GETAREA
software is the protein three dimensional (3D) structure, in our case the bovine re-
coverin structural file that we have extracted from the Protein Data Bank (Berman
et al.
2000
), code entry 1REC (Flaherty et al.
1993
).
Depending on parameter setup, the output of GETAREA is the solvent accessible
surface area in different formats (for the entire protein, per residue, per atom type
or per individual atoms for non-hydrogen atoms) or solvation energy respectively.
=
CS
+
