Simulating force-induced conformational transitions in polysaccharides with the SMD replica exchange method

Abstract

Conventional steered molecular dynamics (SMD) simulations do not readily reproduce equilibrium conditions of atomic force microscopy (AFM) stretch and release measurements of polysaccharides undergoing force-induced conformational transitions because of the gap between the timescales of computer simulations ( approximately 1 mus) and AFM measurements ( approximately 1 s). To circumvent this limitation, we propose using the replica exchange method (REM) to enhance sampling during SMD simulations. By applying REM SMD to a small polysaccharide system and comparing the results with those from AFM stretching experiments, we demonstrate that REM SMD reproduces the experimental results not only qualitatively but quantitatively, approaching near equilibrium conditions of AFM measurements. As tested in this work, hysteresis and computational time of REM SMD simulations of short polysaccharide chains are significantly reduced as compared to regular SMD simulations, making REM SMD an attractive tool for studying forced-induced conformational transitions of small biopolymer systems.

FIGURE 1

A comparison between force-extension curves of dextran obtained by AFM, REM SMD, and regular SMD simulations.

FIGURE 2

Conformational dynamics of ring 5 from regular SMD simulations. (A and B) Dihedral angles O6-C6-C5-O5 (black trace) and O1-C1-C2-O2 (red trace) during (A) 800 ns regular SMD stretching process and (B) 600 ns regular SMD relaxing process. (C and D) Time evolution of the structure of ring 5 from (C) stretching process and (D) relaxing process. The values of the dihedral angle O6-C6-C5-O5 are shown in black, dihedral angle O1-C1-C2-O2 in red, and O1-O6 distance in blue. The direction of the arrows denotes whether it is a stretching or relaxing process.

FIGURE 3

Conformational dynamics of ring 5 from the REM SMD simulations. (A and B) Dihedral angles O6-C6-C5-O5 (black trace) and O1-C1-C2-O2 (red trace) during (A) 19.2 ns REM SMD stretching process and (B) 19.2 ns REM SMD relaxing process. (C and D) Time evolution of the structure of ring 5 from (C) stretching process and (D) relaxing process. The color code is the same as in Fig. 2, C and D.