As part of H2020 EU project "AGILE", A Collaborative System of Systems Multidisciplinary Design Optimization research approach is presented in this paper. This approach relies on physics-based analysis to evaluate the correlations between the airframe design, as well as propulsion, aircraft systems, aerodynamics, structures and emission, from the early design process, and to exploit the synergies within a simultaneous optimization process. Further, the disciplinary analysis modules from multiple organizations, involved in the optimization are integrated within a distributed framework. The disciplinary analysis tools are not shared, but only the data are distributed among partners through a secured network of framework. In order to enable and to accelerate the deployment of collaborative, large scale design and optimization frameworks, the "AGILE Paradigm", a novel methodology, has been formulated during the project. The main elements composing the AGILE Paradigm are the Knowledge Architecture (KA), and the Collaborative Architecture (CA). The first formalizes the overall product development process in a multi-level structure. The latter formalizes the collaborative process within the entire supply chain, and defines how the multiple stakeholders interact with each other.The current paper is focused on the application of using the AGILE Paradigm to solve system of stystems MDO on a regional jet transport aircraft. The focus of the current research paper is: 1) Creation of a system of systems frame work using AGILE Paradigm to support multidisciplinary distributive analysis capability. The framework involves physics based modules such as : Airframe synthesis, aerodynamics, structures, aircraft systems , propulsion system design, nacelle design, nacelle airframe integration, aircraft mission simulation,costs and emissions. 2) Validate the frame work with case study of a regional jet reference aircraft. 3) Assess the sensitivity and coupling of design parameters, local disciplinary optimizataion and its effect on global optimization objectives or constraints. The effects of varying Bypass Ratio (BPR) of engine, offtake effects due to degree of electrification and nacelle effects are propagated through the AGILE MDO framework and presented.