TY - JOUR

T1 - Parallel-pulling protocol for free-energy evaluation

AU - Ngo, Van A.

PY - 2012/3/13

Y1 - 2012/3/13

N2 - Jarzynski's equality (JE) allows us to compute free-energy differences from distributions of work. In molecular dynamics simulations, the traditional way of constructing work distributions is to perform as many pulling simulations as possible. But reliable work distributions are not always produced in a finite number of simulations. The computational cost of using JE is not less than other commonly used methods such as thermodynamic integration and umbrella sampling methods. Here we first show a different proof of JE based on the idea of stepwise pulling procedures that is efficient in computing free energies by using JE. The key point in our proof is that the processes of turning on or off a harmonic potential to perform work are described by double Heaviside functions of time. We then show that the distributions of work performed by the potential can be easily generated from the distributions of a reaction coordinate along a pathway. Based on the proof, we propose sequential and parallel stepwise pulling protocols for generating work distributions that require suitable relaxation time at each pulling step. The criterion for reliable work distributions is that there must be sufficient mutual overlaps between the adjacent distributions of the reaction coordinate along the pathway. We arrive at an alternative formula (besides JE) to compute free-energy differences from the averaged values of the reaction coordinate. The combination of JE and the alternative formula provides a viable way to determine the accuracy of computed free-energy differences. For the stretching of a deca-alanine molecule, our approach requires 21 parallel simulations and relaxation time as small as 0.4 ns for each simulation to estimate free-energy differences with an uncertainty of about 13%.

AB - Jarzynski's equality (JE) allows us to compute free-energy differences from distributions of work. In molecular dynamics simulations, the traditional way of constructing work distributions is to perform as many pulling simulations as possible. But reliable work distributions are not always produced in a finite number of simulations. The computational cost of using JE is not less than other commonly used methods such as thermodynamic integration and umbrella sampling methods. Here we first show a different proof of JE based on the idea of stepwise pulling procedures that is efficient in computing free energies by using JE. The key point in our proof is that the processes of turning on or off a harmonic potential to perform work are described by double Heaviside functions of time. We then show that the distributions of work performed by the potential can be easily generated from the distributions of a reaction coordinate along a pathway. Based on the proof, we propose sequential and parallel stepwise pulling protocols for generating work distributions that require suitable relaxation time at each pulling step. The criterion for reliable work distributions is that there must be sufficient mutual overlaps between the adjacent distributions of the reaction coordinate along the pathway. We arrive at an alternative formula (besides JE) to compute free-energy differences from the averaged values of the reaction coordinate. The combination of JE and the alternative formula provides a viable way to determine the accuracy of computed free-energy differences. For the stretching of a deca-alanine molecule, our approach requires 21 parallel simulations and relaxation time as small as 0.4 ns for each simulation to estimate free-energy differences with an uncertainty of about 13%.

UR - http://www.scopus.com/inward/record.url?scp=84859013740&partnerID=8YFLogxK

U2 - 10.1103/PhysRevE.85.036702

DO - 10.1103/PhysRevE.85.036702

M3 - Article

AN - SCOPUS:84859013740

SN - 1539-3755

VL - 85

JO - Physical Review E - Statistical, Nonlinear, and Soft Matter Physics

JF - Physical Review E - Statistical, Nonlinear, and Soft Matter Physics

IS - 3

M1 - 036702

ER -