Progress update #1: The multiscale pathway mapper & Intergrator

Progress update #1: The multiscale pathway mapper & Intergrator

The first part of the framework is the multiscale pathway mapper & intergrator. It connects four levels of biology in a single chain, so a change at the molecule can be followed all the way to the whole body. Each level is built with a specific method.

At the molecular level, binding free energy, electrostatic complementarity and conditional dissociation are calculated with closed-form thermodynamic and electrostatic formulations. Henderson-Hasselbalch ionization models handle pH-dependent behavior. Where a 3D structure is needed, all-atom coordinates are reconstructed with NeRF and checked for atomic clashes with MolProbity.

At the pathway level, curated pathways from Reactome are separated into beneficial routes and liability routes. A pathway modulation model, written as ordinary differential equations, simulates substrate accumulation, product depletion and compensatory feedback bypasses.

At the tissue level, candidates are scored with quantitative efficacy indices in diseased compartments and safety margins in protected ones.

At the organ level, free drug concentrations feed a 14-compartment whole-body PBPK simulator. It uses lumped compartmental equations for vascular transport, tissue partitioning, hepatic clearance and renal elimination.

The stiff equations at the pathway and organ levels are integrated with LSODA and Radau solvers from SciPy. Each level passes its output to the next.