TY - JOUR
T1 - Advantages of Multidimensional Biasing in Accelerated Dynamics
T2 - Application to the Calculation of the Acid pKa for Acetic Acid
AU - Guo, Jiasen
AU - Albesa, Alberto
AU - Wexler, Carlos
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/10/5
Y1 - 2023/10/5
N2 - The use of accelerated sampling methods such as metadynamics has shown a significant advantage in calculations that involve infrequent events, which would otherwise require sampling a prohibitive number of configurations to determine the difference in free energies between two or more chemically distinct states such as in the calculation of acid dissociation constants Ka. In this case, the most common method is to bias the system via a single collective variable (CV) representing the coordination number of the proton donor group, which yields results in reasonable agreement with experiments. Here we study the deprotonation of acetic acid using the reactive force field ReaxFF and observe a significant dependence of Ka on the simulation box size when biasing only the coordination number CV, which is due to incomplete sampling of the deprotonated state for small simulation systems and inefficient sampling for larger ones. Incorporating a second CV representing the distance between the H3O+ cation and the acetate anion results in substantially more efficient sampling, both accelerating the dynamics and virtually eliminating the computational box size dependence.
AB - The use of accelerated sampling methods such as metadynamics has shown a significant advantage in calculations that involve infrequent events, which would otherwise require sampling a prohibitive number of configurations to determine the difference in free energies between two or more chemically distinct states such as in the calculation of acid dissociation constants Ka. In this case, the most common method is to bias the system via a single collective variable (CV) representing the coordination number of the proton donor group, which yields results in reasonable agreement with experiments. Here we study the deprotonation of acetic acid using the reactive force field ReaxFF and observe a significant dependence of Ka on the simulation box size when biasing only the coordination number CV, which is due to incomplete sampling of the deprotonated state for small simulation systems and inefficient sampling for larger ones. Incorporating a second CV representing the distance between the H3O+ cation and the acetate anion results in substantially more efficient sampling, both accelerating the dynamics and virtually eliminating the computational box size dependence.
UR - http://www.scopus.com/inward/record.url?scp=85173556242&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcb.3c03795
DO - 10.1021/acs.jpcb.3c03795
M3 - Article
C2 - 37738501
AN - SCOPUS:85173556242
SN - 1520-6106
VL - 127
SP - 8446
EP - 8455
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 39
ER -