Functional biodynamics theory and algorithms for inhibitor or activator effectors and their interactions, by computer simulation bioinformatics for translational medicine

Abstract

The conventional bottom‐to‐up approach of R&D is usually: aims, design, findings, data analysis, statistics, and conclusions or suggestive hypothesis. The experimental findings need to fitting empirical curves, formula, or model. The alternative nonconventional, top‐to‐down approach,shown here, is the mathematical system analysis to derive the unified general pharmacodynamics theory/equation/algorithm (PD) based on mass‐action law (MAL)for automated computer simulation. Thus, the approach allows using small number of dose‐data–points to fit the unified MAL‐PD theory/algorithm, for the efficient, cost‐effective automated computer simulation to achieve quantitative/ indexed bioinformatics (BI) diagnostic simulations and conclusions. The median‐effect equation (MEE) or its plot (MEP)is the unified general theory of the MAL fordose‐effect biodynamics/pharmacodynamics (BD/PD), where “dose” can be drugs, biologicals, hormones, modulators, infecting agents, radiation, or UV; and the ”effect” can be inhibitors, activators, in cells, tissues, organs, diseases, animals or in clinical trials. The MAL algorithms also leads to the derivation of the general combination index equation (CIE) with its Fa‐CI plot and Isobologram for BI, that allow the quantification of Synergism (CI<1), Additive effect (CI=1) and Antagonism (CI>1) at different‐effect, or different effect levels. The unique features of MAL‐PD approach are: (A) All terms of the MEE and CIEof the MAL‐PD equations are “dimensionless relativity ratio”,therefore, MAL‐theory is validregardless of units, mode or mechanism of actions of effector(s), and the target systems. (B) The MEE with its MEP, linearizes dose‐effect curves into straight lines,and thereby MEP leads to the “Two Dose‐Data‐Points Minimum Theory”,where the 3rd point is dose zero, and the 4th dose‐point is Dm, which is the universal reference‐point and dynamic‐order common‐link. Thus, particularly useful in animal studies or clinical trials which rarely tolerated over 3 (or more) “dose‐data points” with acceptable dose‐rage and dose density; (C)MAL theory/algorithm allows the samegeneral MAL‐principle to bridge between the basic in vitro/animal studies and the clinical trials. In conclusion, the MAL‐BD/PD/BI/CI approach/theory/algorithm/method serves as the general largest‐common‐denominator forsimplifying the complexity and diversity of biological systems, with automated simulations. This MAL “top to down” innovation provides a new avenue forbiomedical R&D, and for drug evaluations, which is simple, quantitative, efficient and cost‐effective.