Methods of configuring a cooling subassembly for an electronics system are provided, that is, for establishing a coolant-carrying tube layout for interconnecting multiple liquid-cooled cold plates in series-fluid communication for cooling multiple heat-generating electronic components of an electronics system. The electronic components are to be plugged in fixed relation into a preconfigured motherboard, and the tube layout includes at least one rigid coolant-carrying tube. Simplified analysis is initially performed to evaluate stress on the rigid tube(s) and determine if loss of actuation load on the electronic components exceeds an acceptable threshold, and if so, at least one tube having high stress is identified and reconfigured. Thereafter, analysis is performed to determine whether, with available actuation load on the cooling subassembly, electrical connection loading between the electronic components and the supporting motherboard is above an acceptable minimum level. If so, the coolant-carrying tube layout is chosen as a final design.