Musings on mechanism: quest for a quark theory of proteins?

Abstract

The give and take between biology and physics is an important part of the history of modern science, with this partnership perhaps now more intimate than ever. In this essay, I explore the ways in which these different fields can strengthen each other through their distinct outlooks on some of the most important questions being asked about the living world. In particular, I highlight three areas where the perspective from physics might lead to deeper insights into the workings of cells. First, I consider what it means for two ostensibly unrelated problems to be the same, and how such sameness can provide unexpected insights into apparently unrelated phenomena. Second, I consider different conceptions of what constitutes a mechanistic understanding of a given phenomenon with an emphasis on nonmolecular notions of mechanism. The third idea is the importance of "toy problems" as a way of providing foundational insights into the real problems. Though my focus here is primarily on ways in which physics approaches might prove interesting in biology, I close with an example of how biology might substantially alter physics by providing a forum and the tools to uncover a fundamental understanding of nonequilibrium phenomena.-Phillips, R. Musings on mechanism: quest for a quark theory of proteins?

“Essentially, all models are wrong, but some are useful”—a cross-disciplinary agenda for building useful models in cell biology and biophysics

“…Attaining this fluency in both approaches requires time and practice. The path is not always easy because researchers in traditional disciplines too often consider cross-disciplinary projects as not Bpure^enough for their discipline (Parsegian 1997), are uncomfortable with the intrinsically Bdirty^nature of experimental data, or under-appreciate that fluency in multiple fields is more than the sum of its parts, and can lead to the creation of new branches of physics, mathematics, and biology (Phillips 2017). From experience, we think this effort is worth the trouble.…”

“…Theory (or theoretical models) is a set of mathematical equations that describe the biological system. Theory usually aims to explicitly determine how key properties of the biological system change with parameter values or to identify critical parameters and relationships between parameters which define different regimes, by deriving formulas from the model equations, without running simulations (Howard 2014;Phillips 2015Phillips , 2017. However, such closed formulas are usually very difficult (or even impossible) to obtain except in specific cases of models that have a low number of variables and parameters, or at the cost of certain simplifications.…”

“…The level of detail of the model closely depends on the question asked and the experimental data available. If the model is more detailed than the available data, there is a high risk to make many arbitrary choices and speculations, and the model will have too many unknown parameters (Phillips 2017). Conversely, if the model is too coarse, it may miss features that are important to answer the biological question asked.…”

Data analysis to modeling to building theory in NK cell biology and beyond: How can computational modeling contribute?

“…There is a multitude of processes that work together to relay changes from the smallest to the largest scales in these systems. Mathematical models, often providing a reduced or a coarse‐grained description of these physical processes, become essential to describe such multiscale systems . Reduced models have been successful in describing several aspects of NK cell and leukocyte biology, in particular for signaling and development in NK cells, and evolution of NKR repertoires.…”

“…Mathematical models, often providing a reduced or a coarse-grained description of these physical processes, become essential to describe such multiscale systems. [8][9][10][11] Reduced models have been successful in describing several aspects of NK cell and leukocyte biology, in particular for signaling and development in NK cells, and evolution of NKR repertoires. These models are discussed in Section 1.…”