Department of Physics, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
J Chem Phys. 2020 Dec 28;153(24):244119. doi: 10.1063/5.0033405.
Free energy differences are a central quantity of interest in physics, chemistry, and biology. We develop design principles that improve the precision and accuracy of free energy estimators, which have potential applications to screening for targeted drug discovery. Specifically, by exploiting the connection between the work statistics of time-reversed protocol pairs, we develop near-equilibrium approximations for moments of the excess work and analyze the dominant contributions to the precision and accuracy of standard nonequilibrium free-energy estimators. Within linear response, minimum-dissipation protocols follow the geodesics of the Riemannian metric induced by the Stokes friction tensor. We find that the next-order contribution arises from the rank-3 supra-Stokes tensor that skews the geometric structure such that minimum-dissipation protocols follow the geodesics of a generalized cubic Finsler metric. Thus, near equilibrium, the supra-Stokes tensor determines the leading-order contribution to the bias of bidirectional free-energy estimators.
自由能差是物理学、化学和生物学中一个核心的关注点。我们制定了设计原则，提高了自由能估计器的精度和准确性，这对于靶向药物发现的筛选具有潜在的应用价值。具体来说，通过利用时间反转协议对的工作统计之间的联系，我们为超额工作的矩开发了近平衡近似，并分析了标准非平衡自由能估计器的精度和准确性的主要贡献。在线性响应范围内，最小耗散协议遵循由 Stokes 摩擦张量诱导的黎曼度量的测地线。我们发现，下一个阶贡献来自于秩为 3 的超 Stokes 张量，它扭曲了几何结构，使得最小耗散协议遵循广义三次 Finsler 度量的测地线。因此，在近平衡状态下，超 Stokes 张量决定了双向自由能估计器偏差的主要贡献。
