Investigation of coupling between collective dynamics and function of enzymes

Abstract

To bridge the structure and function of an enzyme through dynamics is an important problem in protein science. For this aim, the vibrational dynamics for a set of enzymes with different biological units and fold types are studied by the anisotropic network model (ANM). All of these enzymes carry at least one functional loop that closes over the active site during catalysis, for which open and closed loop crystal structures have been determined experimentally. The collective dynamics of these enzymes, which are based on the slow modes of motion from ANM, reveal close coupling with the closure of the specific functional loops. Overlap values are calculated to compare ANM findings with the experimentally observed deformations between open and closed structures. The functional loop closure is detected in at least one of the slowest ten modes for all enzymes. Also, atomic fluctuations of the active site residues in triosephosphate isomerase (TIM) and trypsin are investigated by atomistic ANM and principal component analysis of molecular dynamics simulations. Changes in specific interatomic distances in low frequency modes indicate the possibility of collective vibrations promoting certain steps of proposed reaction mechanisms. First step and Mechanism A proposed for second step of TIM reaction is found to be coupled with slow modes in ANM and PCA calculations.