Chapter 3 Fishing for Functional Motions with Elastic Network Models

Abstract

Publisher Summary Simulations of large macromolecules and long time-scale motions that are inaccessible to conventional molecular dynamics (MD) simulation procedures are now routinely performed using normal mode analysis (NMA) of elastic network (EN) models. In addition to the recent impact in refining experimental data, two applications of EN models that appear to have great potential for impact in computational biology are high-throughput analysis of multiple structures and coupling EN modes to MD simulations. Specifically, the identification of similarities among motions for protein (super)families point to the underlying, evolutionarily conserved key features. The combination of EN models and MD simulations hold much promise because the former are able to explore conformational space efficiently and the latter contain atomic specificity. Simulations using amplified collective modes have characterized extremely large-scale, non-equilibrium folding motions suggesting a wide range of possible applications. Other molecular dynamics procedures that rely upon a pathway among states, such as milestoning or transition path sampling, could benefit from widely spaced pathway points generated by EN models.