Curiously, (and also perhaps ridiculously), it just occurred to me, that designing a successfully folding RNA for the Lab is perhaps not unlike the challenge of creating a suitable seating arrangement for a huge political dinner party, where all the guests are of different races, creeds, colors, nationalities, political views, sexual orientations, and many of whom also speak no one language in common. Some of the guests of different groups get along fabulously, have at least one language in common, share reasonably compatible world views, and some even really genuinely LIKE one another. However, members of some groups have so little common ground with certain others, that they can barely tolerate being in the same room with members of these groups, much less tolerate being seated directly across the table from one.
So the task and challenge becomes - almost totally - “How can I create an arrangement that everyone at the table can tolerate?” Because if I cannot, some guests may push their chairs back from the table in a gesture of dissatisfaction (creating a bulge), or others may object so strenuously, that they get up and move their entire section of the table to another location (totally destroying the carefully planned-out [and mandatory] table arrangement).
Corollary questions become “How can I arrange the seating to accommodate the incompatibles?” …and “Which guests may act as diplomatic intermediaries between otherwise incompatible guests, and allow me to achieve a workable, if reluctant peace?” …and “How many of each group absolutely MUST be invited, as a minimum, to achieve sufficient political balance,and provide for profitable exchanges to occur?”
Fortunately, we have some influence over who gets invited at all, but we MUST fill up all the seats, and if we do not have a sufficiently diverse group, the goal of communication between political adversaries will not be achieved.
Okay, I know that many may view this analogy as a little silly, and that I may easily incur some not completely undeserved criticism (if not outright ridicule) for making a “political dinner seating arrangement” problem out of a serious scientific endeavor.
The more I think about this analogy, the more the concepts of location, relative position, and orientation begin to take on prime importance of what factors must be considered in both this analogous “seating arrangement,” and in actual RNA design in the Lab…
And as I think about it even more, the parallels become more and more apparent and undeniable, and the analogy more and more useful as a tool for increasing understanding of how to achieve the goal: the creation of a workable arrangement of diverse, only marginally compatible entities - to fulfill a larger purpose.
There is something about anthropomorphizing an abstract problem, that tends to make it more accessible to human intuitive faculties, I think.
Please leave feedback to let me know if this analogy sparked any positive response in your conceptualization process and whether this reduction to human terms in any way clarifies or illumines the way you think you may approach Lab RNA design problems in the game going forward.
I’d also love to hear others opinions and ideas for alternate, perhaps superior analogies, as this type of metaphorical comparative analogy definitely aids my whole inner landscape of understanding, as well as my inner process of problem-solving.
Thanks, and Best Regards,