Abstract
We propose here a working unit for teaching basic concepts of structural bioinformatics and evolution through the example of a wooden snake puzzle, strikingly similar to toy models widely used in the literature of protein folding. In our experience, developed at a Master’s course at the Universidad Autónoma de Madrid (Spain), the concreteness of this example helps to overcome difficulties caused by the interdisciplinary nature of this field and its high level of abstraction, in particular for students coming from traditional disciplines. The puzzle will allow us discussing a simple algorithm for finding folded solutions, through which we will introduce the concept of the configuration space and the contact matrix representation. This is a central tool for comparing protein structures, for studying simple models of protein energetics, and even for a qualitative discussion of folding kinetics, through the concept of the Contact Order. It also allows a simple representation of misfolded conformations and their free energy. These concepts will motivate evolutionary questions, which we will address by simulating a structurally constrained model of protein evolution, again modelled on the snake puzzle. In this way, we can discuss the analogy between evolutionary concepts and statistical mechanics that facilitates the understanding of both concepts. The proposed examples and literature are accessible, and we provide supplementary material (see ‘Data Availability’) to reproduce the numerical experiments. We also suggest possible directions to expand the unit. We hope that this work will further stimulate the adoption of games in teaching practice.
Highlights
Scientific knowledge is becoming increasingly interdisciplinary, with life sciences being one of the most significant examples
One important aspect in which we focused in the development of these problems is the intimate relation between physics and evolution
By comparing the Contact Divergence in protein structure space with the Poissonian distance between the corresponding sequences, we found that structure evolution is slower than sequence evolution by a factor that ranges from 0.24 to 0.37 for different superfamilies (Pascual-García et al, 2010)
Summary
Scientific knowledge is becoming increasingly interdisciplinary, with life sciences being one of the most significant examples. There are long regions of consecutive blocks of length 2 that can provide the opportunity to discuss the role of more flexible regions in real proteins such as large loops or intrinsically unstructured regions After this preliminary descriptive analysis of the puzzle we propose the first computational exercise, which consists in programming a search algorithm that generates all the maximally compact conformations (i.e., the solutions of the snake puzzle folded in a cube). For the sake of simplicity, we will limit our computations to the solutions of the snake puzzle This is analogous to the toy model of protein folding based on the maximally compact structures on the cubic lattice introduced by Shakhnovich and coworkers in the 90’s (Shakhnovich & Gutin, 1990). Three structures are too few to test this behaviour, but it is interesting that there are
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