Steered molecular dynamics analysis of the role of cofilin in increasing the flexibility of actin filaments

Abstract

Cofilin is one of the most essential regulatory proteins and participates in the process of disassembling actin filaments. Cofilin induces conformational changes to actin filaments, and both the bending and torsional rigidity of the filament In this study, we investigate the effects of cofilin on the mechanical properties of actin filaments using computational methods. Three models defined by their number of bound cofilin are constructed using coarse-grained MARTINI force field, and they are then extended with steered molecular dynamics simulation. After obtaining the stress-strain curves of the models, we calculate their Young's moduli and other mechanical properties that have not yet been determined for actin filaments. We analyze the cause of the different behaviors of the three models based on their atomistic geometrical differences. Finally, it is demonstrated that cofilin binding causes changes in the distances, angles, and stabilities of the residues in actin filaments. (C) 2016 Elsevier B.V. All rights reserved.