Fiber Fabry-Perot microcavities (FFPCs) enhance light-matter interactions by localizing light in time and space. Such FFPCs are at the heart of this powerful detection scheme exploiting photothermal nonlinearities and Pound-Drever-Hall frequency locking that enabled label-free profiling of single solution-phase biomolecules with unprecedented sensitivity. Here, we deploy a combination of experiment and simulation to provide a quantitative mechanism for the observed single-molecule sensitivity and achieve quantitative agreement with experiment. A key element of the mechanism is maintaining the FFPC in an unstable regime and allowing it to rapidly shift between hot and cold photothermal equilibria upon perturbation. We show how Brownian molecular trajectories, introducing resonance fluctuations less than 1000th of the already narrow microcavity line width, can produce selective and highly amplified responses. Such perturbations are found to exist in a specific and tunable frequency window termed the molecular velocity filter window. The model's predictive capacity suggests it will be an important tool to identify additional modes of sensitivity to single-molecule hydrodynamic behavior.