"Decoupling the Pharmacological Fallacy of Mono-Target Screenings: A Multi-Dimensional In Silico Matrix Targeting Bio-Synthetic Pathways in Complex Cellular Systems"

ABSTRACT- Targeted single drug screening dominates, the current landscape for drug discovery, yet it offers a very poor representation of in vivo drug action when applied to complex human cells. I demonstrate how paradigm of mono-target screening yielding high attrition and missed potential can be challenged by my multi-dimensional in silico matrix, which moves beyond the one-protein-one-compound assumption. Rather than it sequentially targeting a single protein, my model properly assesses how compounds influence intercommunicating biosynthetic cascades, by mapping the interplay of multiple novel compounds across shared pathways. For constructed by integrating concepts from network pharmacology, molecular docking and pathway analysis, the multi-dimensional cell construct model perfectly allows integrative assessment of multiple cellular nodes. When it applied to disease models based on a convergent cascade of metabolic pathways, the cell matrix identified synergistic modulators that would not have been found in standard mono-target screens. The Subsets of compounds with very poor single-target activity have accumulated multi-target activity, destabilizing entire pathways. My model properly reduced false-negatives and accurately predicted biologically relevant off target effects, by providing a first step toward deploying cell matrix models to promote successful drug discovery. Keywords- Polypharmacology, Multitarget Screening by insilico model, Biosynthetic Pathways, Network Analysis, Drug Discovery