Applying Mechanical Analysis Tools to the Study of Allosteric Regulation Pathways in Proteins

Allostery is a phenomenon in which the function of a protein is regulated by the propagation of a signal via small conformational changes. Allostery plays a key role in many mechanistic pathways in biology, and for this reason, knowledge on how to analyze allosteric proteins and predict pathways of allostery has a wide range of potential applications, including drug design and protein engineering. Because many of the conformational changes involved in protein allostery include small deformations at a local level, we hypothesize that knowledge of the modulus of elasticity at each atom position or within specific regions in a protein can provide valuable information about the local mobility and stability under conformational deformations. Here, we expand to the analysis of allosteric proteins, a method previously developed to calculate local elastic moduli at different positions in a material (J. Chem. Phys. 128, 224504 (2008)), in order to build a 3D map of local mechanical properties that can be used to identify pathways of allostery in proteins and protein networks. We apply this method to the analysis of a preliminary set of allosteric proteins, and compare our results to previous ones reported from both computational and experimental studies.