3 research outputs found
Protein Dynamics and Contact Topology Reveal Protein–DNA Binding Orientation
Structure-encoded conformational
dynamics are crucial for biomolecular
functions. However, there is insufficient evidence to support the
notion that dynamics play a role in guiding protein-nucleic acid interactions.
Here, we show that protein–DNA docking orientation is a function
of protein intrinsic dynamics, but the binding site itself does not
display unique patterns in the examined spectrum of motions. This
revelation is made possible by a novel technique that locates “dynamics
interfaces” in proteins across which protein parts are anticorrelated
in their slowest dynamics. A striking statistic is that such interfaces
intersect the DNA in 97% of the 104 examined cases. These findings
were then used to screen decoys generated by rigid-body docking of
DNA molecules onto DNA-binding proteins. Using our method, the chance
to discern near-native poses from non-native decoys increased by 2.5-
and 1.6-fold, as compared to a random guess and methods based on surface
complementarity, respectively. Hence, dynamically allowed protein–DNA
docking orientations can work as new filters to cull and rerank docking
poses and therefore enhance the predictability of DNA-binding sites
that themselves do not have distinct dynamics features. Computer software
implementing the method can be accessed via http://dyn.life.nthu.edu.tw/IDD/DNA.htm
Protein Dynamics and Contact Topology Reveal Protein–DNA Binding Orientation
Structure-encoded conformational
dynamics are crucial for biomolecular
functions. However, there is insufficient evidence to support the
notion that dynamics play a role in guiding protein-nucleic acid interactions.
Here, we show that protein–DNA docking orientation is a function
of protein intrinsic dynamics, but the binding site itself does not
display unique patterns in the examined spectrum of motions. This
revelation is made possible by a novel technique that locates “dynamics
interfaces” in proteins across which protein parts are anticorrelated
in their slowest dynamics. A striking statistic is that such interfaces
intersect the DNA in 97% of the 104 examined cases. These findings
were then used to screen decoys generated by rigid-body docking of
DNA molecules onto DNA-binding proteins. Using our method, the chance
to discern near-native poses from non-native decoys increased by 2.5-
and 1.6-fold, as compared to a random guess and methods based on surface
complementarity, respectively. Hence, dynamically allowed protein–DNA
docking orientations can work as new filters to cull and rerank docking
poses and therefore enhance the predictability of DNA-binding sites
that themselves do not have distinct dynamics features. Computer software
implementing the method can be accessed via http://dyn.life.nthu.edu.tw/IDD/DNA.htm
Molecular Binding Sites Are Located Near the Interface of Intrinsic Dynamics Domains (IDDs)
We provide evidence supporting that
protein–protein and
protein–ligand docking poses are functions of protein shape
and intrinsic dynamics. Over sets of 68 protein–protein complexes
and 240 nonhomologous enzymes, we recognize common predispositions
for binding sites to have minimal vibrations and angular momenta,
while two interacting proteins orient so as to maximize the angle
between their rotation/bending axes (>65°). The findings are
then used to define quantitative criteria to filter out docking decoys
less likely to be the near-native poses; hence, the chances to find
near-native hits can be doubled. With the novel approach to partition
a protein into “domains” of robust but disparate intrinsic
dynamics, 90% of catalytic residues in enzymes can be found within
the first 50% of the residues closest to the interface of these dynamics
domains. The results suggest an anisotropic rather than isotropic
distribution of catalytic residues near the mass centers of enzymes