How to Measure Biomolecular Forces: A “Tug-of-War” Approach Chapter uri icon

abstract

  • Experimental measurements of biomolecular forces are ever-increasing in resolution, which calls for a convenient way of calculating forces as free energy gradients in simulations. While it is possible to first calculate the free energy landscape and take the gradient, free energy simulations typically require very extensive sampling time. Here, a quick and dirty method of calculating force at a given point in the conformational space is presented, named the tug-of-war sampling. Its basic operational principle is the same as an optical trap experiment that traces the position of a microbead held by a focused laser beam: A stiff harmonic sampling potential is applied to the system to constrain the motion at a particular conformational state, and the fluctuation of the constrained part of the molecule around the center of the sampling potential is analyzed to calculate the first and second order gradients of the free energy. The method is local and does not require sampling over multiple points to take the gradient, thus is very efficient. Tutorial-style examples are given. This method likely has broad applications in calculating mechanical forces in macromolecular systems. © 2010 Springer Science+Business Media B.V.

author list (cited authors)

  • Hwang, W.

citation count

  • 0

Book Title

  • Computational Modeling in Biomechanics

publication date

  • January 2010