Improved protein structure prediction using potentials from deep learning

Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence1. This problem is of fundamental importance as the structure of a protein largely determines its function2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction5 (CASP13)—a blind assessment of the state of the field—AlphaFold created high-accuracy structures (with template modelling (TM) scores6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined7

Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13)

We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13 Submissions were made by three free-modelling methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on-par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 free-modelling assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group. (An average GDT_TS of 61.4.) The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 free-modelling domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods

[multi’vocal]: reflections on engaging everyday people in the development of a collective non-binary synthesized voice

The growing field of Human-Computer Interaction (HCI) takes a step out from conventional screenbased interactions, creating new scenarios, in which voice synthesis and voice recognition become important elements. Such voices are commonly created through concatenative or parametric synthesis methods, which access large voice corpora, pre-recorded by a single professional voice actor. These designed voices arguably propagate representations of gender binary identities. In this paper we present our project, [multi’vocal], which aims to challenge the current gender binary representations in synthesized voices. More specifically we explore if it is possible to create a non-binary synthesized voice through engaging everyday people of diverse backgrounds in giving voice to a collective synthesized voice of all genders, ages and accents

Correlated topographic analysis: estimating an ordering of correlated components

Abstract This paper describes a novel method, which we call correlated topographic analysis (CTA), to estimate non-Gaussian components and their ordering (topography). The method is inspired by a central motivation of recent variants of independent component analysis (ICA), namely, to make use of the residual statistical dependency which ICA cannot remove. We assume that components nearby on the topographic arrangement have both linear and energy correlations, while far-away components are statistically independent. We use these dependencies to fix the ordering of the components. We start by proposing the generative model for the components. Then, we derive an approximation of the likelihood based on the model. Furthermore, since gradient methods tend to get stuck in local optima, we propose a three-step optimization method which dramatically improves topographic estimation. Using simulated data, we show that CTA estimates an ordering of the components and generalizes a previous method in terms of topography estimation. Finally, to demonstrate that CTA is widely applicable, we learn topographic representations for three kinds of real data: natural images, outputs of simulated complex cells and text data