%0 Journal Article
%T Connecting Femtosecond Motions to Pharmacological Outcomes through a Multiscale Architecture for Residence Time, Allostery, and Functional Response
%A Sofía Martínez
%A Carlos Gómez
%A Lucia Navarro
%J International Journal of Pharmaceutical Research and Allied Sciences
%@ 2277-3657
%D 2025
%V 14
%N 1
%R 10.51847/haQ6MUGaAS
%P 35-45
%X Molecular pharmacology spans a temporal range that extends from femtosecond-scale bond and electronic motions to clinical-scale patterns of exposure, efficacy, and failure. The central difficulty is not merely computational cost. It is the absence of a disciplined architecture for deciding when information obtained at one scale can legitimately constrain claims at another. This article proposes the Temporal–Mechanistic Translation Architecture, an original conceptual synthesis that connects molecular motion, metastable conformational ensembles, kinetic transitions, residence time, allosteric communication, signalling, and systems-level functional response. The architecture is organized as six linked layers separated by explicit validation gates. Each gate specifies the evidence required to move from one inferential level to the next and prevents thermodynamic, kinetic, structural, functional, and translational quantities from being treated as interchangeable. The framework introduces three governing principles: adjacent-scale validation, bidirectional consistency, and decision-bounded interpretation. It further derives testable propositions concerning state definition, kinetic bottlenecks, residence-time surrogates, allosteric transmission, functional coupling, and exposure-dependent response. Validation is treated as a staged process requiring trajectory stability, kinetic reproducibility, orthogonal experimental constraint, perturbational testing, identifiability analysis, and prospective decision evaluation. The architecture does not claim that atomistic simulation can independently predict pharmacological outcomes, nor does it imply clinical, regulatory, or deployment readiness. Its intended contribution is to organize mechanistic reasoning, expose hidden assumptions, identify failure points, and define the evidence needed before a cross-scale explanation can be treated as decision-relevant.
%U https://ijpras.com/article/connecting-femtosecond-motions-to-pharmacological-outcomes-through-a-multiscale-architecture-for-res-epsynnv53rgf5nb