structure, one has to keep in mind that how well the structure resolution condition
matches with the actual functioning condition of the receptor and resolution of the
structure [14]. Apart from this, many questions may arise like whether the structure
is ligand bound? Whether active conformation of the structure is solved? Whether
the structure is solved at pH similar to the functioning pH? These can also be of
importance to consider during docking. The receptor crystal structure selection has
to be done with care considering the quality of the structure model. Some of the
most important parameters for crystal structure assessment have been outlined in
the literature [45] and listed in Table 1. Crystal structure resolution which is a
measure of quality of electron density data collected is one of such parameters;
structures resolved at less than 1 Å are considered high-quality one being able to
resolve electron densities at atomic level while structures greater than 3 Å have
smeared electron densities and atomic positions are not clearly identifiable. Hence,
crystal structure with resolution in range: 1 Å < resolution < 3 Å can be
Table 1 List of important parameters for assessing quality of X-ray crystal structure
Parameter
Description
Preferred Comment
Electron density and solved model quality
r-cutoff
r-cutoff applied to the data
None
Lower
resolution
A minimum spacing (d) of crystal lattice planes that
still provide measurable diffraction of X-rays.
20–50 Å
Higher
resolution
A minimum spacing (d) of crystal lattice planes that
still provide measurable diffraction of X-rays and
also hI=r I
ð Þi greater than 2 in high-resolution shell.
<3 Å
Higher is
better
Completeness
The number of observed reflections divided by the
theoretical maximum
*100% Higher is
better
hI=r I
ð Þi
The average ratio of reflection intensity to its
estimated error. Signal-to-noise ratio
>2
R-factor
A measure of the global reliability factor or
goodness-of-fit between the experimentally obtained
structure factor amplitudes, F obs , and the calculated
structure factor amplitudes, F calc , obtained from the
model.
<25%
Smaller
is better
R free –R-factor
R free is R-factor for random *5% reflections, not
used for model refinement. R free − R-factor < 2, may
be indication of overfitting while R free − Rfactor > 7 may be due to poor refinement of model
2–7%
Smaller
is better
R O2A
Observation to atom ratio
Higher is
better
Geometric parameters of model quality
RMSD (bonds) Root mean square deviation of bond lengths from
ideal values
0.15–
0.25 Å
RMSD (angles) Root mean square deviation of bond angles from
ideal values
1°–3°
Ramachandran
violations
Number of /–w torsion pairs falling in disallowed
regions of Ramachandran plot
0
Smaller
is better
In Silico Structure-Based Prediction of Receptor–Ligand Binding …
117
matches with the actual functioning condition of the receptor and resolution of the
structure [14]. Apart from this, many questions may arise like whether the structure
is ligand bound? Whether active conformation of the structure is solved? Whether
the structure is solved at pH similar to the functioning pH? These can also be of
importance to consider during docking. The receptor crystal structure selection has
to be done with care considering the quality of the structure model. Some of the
most important parameters for crystal structure assessment have been outlined in
the literature [45] and listed in Table 1. Crystal structure resolution which is a
measure of quality of electron density data collected is one of such parameters;
structures resolved at less than 1 Å are considered high-quality one being able to
resolve electron densities at atomic level while structures greater than 3 Å have
smeared electron densities and atomic positions are not clearly identifiable. Hence,
crystal structure with resolution in range: 1 Å < resolution < 3 Å can be
Table 1 List of important parameters for assessing quality of X-ray crystal structure
Parameter
Description
Preferred Comment
Electron density and solved model quality
r-cutoff
r-cutoff applied to the data
None
Lower
resolution
A minimum spacing (d) of crystal lattice planes that
still provide measurable diffraction of X-rays.
20–50 Å
Higher
resolution
A minimum spacing (d) of crystal lattice planes that
still provide measurable diffraction of X-rays and
also hI=r I
ð Þi greater than 2 in high-resolution shell.
<3 Å
Higher is
better
Completeness
The number of observed reflections divided by the
theoretical maximum
*100% Higher is
better
hI=r I
ð Þi
The average ratio of reflection intensity to its
estimated error. Signal-to-noise ratio
>2
R-factor
A measure of the global reliability factor or
goodness-of-fit between the experimentally obtained
structure factor amplitudes, F obs , and the calculated
structure factor amplitudes, F calc , obtained from the
model.
<25%
Smaller
is better
R free –R-factor
R free is R-factor for random *5% reflections, not
used for model refinement. R free − R-factor < 2, may
be indication of overfitting while R free − Rfactor > 7 may be due to poor refinement of model
2–7%
Smaller
is better
R O2A
Observation to atom ratio
Higher is
better
Geometric parameters of model quality
RMSD (bonds) Root mean square deviation of bond lengths from
ideal values
0.15–
0.25 Å
RMSD (angles) Root mean square deviation of bond angles from
ideal values
1°–3°
Ramachandran
violations
Number of /–w torsion pairs falling in disallowed
regions of Ramachandran plot
0
Smaller
is better
In Silico Structure-Based Prediction of Receptor–Ligand Binding …
117