Elastic models of conformational transitions in macromolecules

We develop a computationally efficient and physically realistic method to simulate the transition of a macromolecule between two conformations. Our method is based on a coarse-grained elastic network model in which contact interactions between spatially proximal parts of the macromolecule are modelled with Gaussian/harmonic potentials. To delimit the interactions in such models, we introduce a cutoff to the permitted number of nearest neighbors. This generates stiffness (Hessian) matrices that are both sparse and quite uniform, hence, allowing for efficient computations. Several toy models are tested using our method to mimic simple classes of macromolecular motions such as stretching, hinge bending, shear, compression, ligand binding and nucleic acid structural transitions. Simulation results demonstrate that the method developed here reliably generates sequences of feasible intermediate conformations of macromolecules, since our method observes steric constraints and produces monotonic changes to virtual bond angles and torsion angles. A final application is made to the opening process of the protein lactoferrin.