Decomposition of Forces in Protein: Methodology and General Properties

In contrast to the central role played by the structure
of biomolecules,
the complementary force-based view has received little attention in
past studies. Here, we proposed a simple method for the force decomposition
of multibody interactions and provided some techniques to analyze
and visualize the general behavior of forces in proteins. It was shown
that atomic forces fluctuate at a magnitude of about 3000 pN, which
is huge in the context of cell biology. Remarkably, the average scalar
product between atomic force and displacement universally approximates
−3kBT. This is smaller by an order of magnitude than the simple product
of their fluctuation magnitudes due to the unexpectedly weak correlation
between the directions of force and displacement. The pairwise forces
are highly anisotropic, with elongated fluctuation ellipsoids. Residue–residue
forces can be attractive or repulsive (despite being more likely to
be attractive), forming some kind of tensegrity structure stabilized
by a complicated network of forces. Being able to understand and predict
the interaction network provides a basis for rational drug design
and uncovering molecular recognition mechanisms.