Proteins perform critical processes in all living systems: converting solar
energy into chemical energy, replicating DNA, as the basis of highly performant
materials, sensing and much more. While an incredible range of functionality
has been sampled in nature, it accounts for a tiny fraction of the possible
protein universe. If we could tap into this pool of unexplored protein
structures, we could search for novel proteins with useful properties that we
could apply to tackle the environmental and medical challenges facing humanity.
This is the purpose of protein design.
Sequence design is an important aspect of protein design, and many successful
methods to do this have been developed. Recently, deep-learning methods that
frame it as a classification problem have emerged as a powerful approach.
Beyond their reported improvement in performance, their primary advantage over
physics-based methods is that the computational burden is shifted from the user
to the developers, thereby increasing accessibility to the design method.
Despite this trend, the tools for assessment and comparison of such models
remain quite generic. The goal of this paper is to both address the timely
problem of evaluation and to shine a spotlight, within the Machine Learning
community, on specific assessment criteria that will accelerate impact.
We present a carefully curated benchmark set of proteins and propose a number
of standard tests to assess the performance of deep learning based methods. Our
robust benchmark provides biological insight into the behaviour of design
methods, which is essential for evaluating their performance and utility. We
compare five existing models with two novel models for sequence prediction.
Finally, we test the designs produced by these models with AlphaFold2, a
state-of-the-art structure-prediction algorithm, to determine if they are
likely to fold into the intended 3D shapes.Comment: 9 pages, 5 figure