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 −3k_BT. 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.