Adrien Treuille

Predicting protein structures with a multiplayer online game

People exert large amounts of problem-solving effort playing computer games. Simple image- and text-recognition tasks have been successfully ‘crowd-sourced’ through games, but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.

Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules

We have recently completed a full re-architecturing of the ROSETTA molecular modeling program, generalizing and expanding its existing functionality. The new architecture enables the rapid prototyping of novel protocols by providing easy-to-use interfaces to powerful tools for molecular modeling. The source code of this rearchitecturing has been released as ROSETTA3 and is freely available for academic use. At the time of its release, it contained 470,000 lines of code. Counting currently unpublished protocols at the time of this writing, the source includes 1,285,000 lines. Its rapid growth is a testament to its ease of use. This chapter describes the requirements for our new architecture, justifies the design decisions, sketches out central classes, and highlights a few of the common tasks that the new software can perform.

Continuum crowds

We present a real-time crowd model based on continuum dynamics. In our model, a dynamic potential field simultaneously integrates global navigation with moving obstacles such as other people, efficiently solving for the motion of large crowds without the need for explicit collision avoidance. Simulations created with our system run at interactive rates, demonstrate smooth flow under a variety of conditions, and naturally exhibit emergent phenomena that have been observed in real crowds.

Fluid control using the adjoint method

We describe a novel method for controlling physics-based fluid simulations through gradient-based nonlinear optimization. Using a technique known as the adjoint method, derivatives can be computed efficiently, even for large 3D simulations with millions of control parameters. In addition, we introduce the first method for the full control of free-surface liquids. We show how to compute adjoint derivatives through each step of the simulation, including the fast marching algorithm, and describe a new set of control parameters specifically designed for liquids.

Near-optimal character animation with continuous control

We present a new approach to realtime character animation with interactive control. Given a corpus of motion capture data and a desired task, we automatically compute near-optimal controllers using a low-dimensional basis representation. We show that these controllers produce motion that fluidly responds to several dimensions of user control and environmental constraints in realtime. Our results indicate that very few basis functions are required to create high-fidelity character controllers which permit complex user navigation and obstacle-avoidance tasks.

Model reduction for real-time fluids

We present a new model reduction approach to fluid simulation, enabling large, real-time, detailed flows with continuous user interaction. Our reduced model can also handle moving obstacles immersed in the flow. We create separate models for the velocity field and for each moving boundary, and show that the coupling forces may be reduced as well. Our results indicate that surprisingly few basis functions are needed to resolve small but visually important features such as spinning vortices.

RNA design rules from a massive open laboratory

Significance Self-assembling RNA molecules play critical roles throughout biology and bioengineering. To accelerate progress in RNA design, we present EteRNA, the first internet-scale citizen science “game” scored by high-throughput experiments. A community of 37,000 nonexperts leveraged continuous remote laboratory feedback to learn new design rules that substantially improve the experimental accuracy of RNA structure designs. These rules, distilled by machine learning into a new automated algorithm EteRNABot, also significantly outperform prior algorithms in a gauntlet of independent tests. These results show that an online community can carry out large-scale experiments, hypothesis generation, and algorithm design to create practical advances in empirical science. Self-assembling RNA molecules present compelling substrates for the rational interrogation and control of living systems. However, imperfect in silico models—even at the secondary structure level—hinder the design of new RNAs that function properly when synthesized. Here, we present a unique and potentially general approach to such empirical problems: the Massive Open Laboratory. The EteRNA project connects 37,000 enthusiasts to RNA design puzzles through an online interface. Uniquely, EteRNA participants not only manipulate simulated molecules but also control a remote experimental pipeline for high-throughput RNA synthesis and structure mapping. We show herein that the EteRNA community leveraged dozens of cycles of continuous wet laboratory feedback to learn strategies for solving in vitro RNA design problems on which automated methods fail. The top strategies—including several previously unrecognized negative design rules—were distilled by machine learning into an algorithm, EteRNABot. Over a rigorous 1-y testing phase, both the EteRNA community and EteRNABot significantly outperformed prior algorithms in a dozen RNA secondary structure design tests, including the creation of dendrimer-like structures and scaffolds for small molecule sensors. These results show that an online community can carry out large-scale experiments, hypothesis generation, and algorithm design to create practical advances in empirical science.

The challenge of designing scientific discovery games

Incorporating the individual and collective problem solving skills of non-experts into the scientific discovery process could potentially accelerate the advancement of science. This paper discusses the design process used for Foldit, a multiplayer online biochemistry game that presents players with computationally difficult protein folding problems in the form of puzzles, allowing ordinary players to gain expertise and help solve these problems. The principle challenge of designing such scientific discovery games is harnessing the enormous collective problem-solving potential of the game playing population, who have not been previously introduced to the specific problem, or, often, the entire scientific discipline. To address this challenge, we took an iterative approach to designing the game, incorporating feedback from players and biochemical experts alike. Feedback was gathered both before and after releasing the game, to create the rules, interactions, and visualizations in Foldit that maximize contributions from game players. We present several examples of how this approach guided the games design, and allowed us to improve both the quality of the gameplay and the application of player problem-solving.

Modular bases for fluid dynamics

We present a new approach to fluid simulation that balances the speed of model reduction with the flexibility of grid-based methods. We construct a set of composable reduced models, or tiles, which capture spatially localized fluid behavior. We then precompute coupling terms so that these models can be rearranged at runtime. To enforce consistency between tiles, we introduce constraint reduction. This technique modifies a reduced model so that a given set of linear constraints can be fulfilled. Because dynamics and constraints can be solved entirely in the reduced space, our method is extremely fast and scales to large domains.

Example-Based Stereo with General BRDFs

This paper presents an algorithm for voxel-based reconstruction of objects with general reflectance properties from multiple calibrated views. It is assumed that one or more reference objects with known geometry are imaged under the same lighting and camera conditions as the object being reconstructed. The unknown object is reconstructed using a radiance basis inferred from the reference objects. Each view may have arbitrary, unknown distant lighting. If the lighting is calibrated, our model also takes into account shadows that the object casts upon itself. To our knowledge, this is the first stereo method to handle general, unknown, spatially-varying BRDFs under possibly varying, distant lighting, and shadows. We demonstrate our algorithm by recovering geometry and surface normals for objects with both uniform and spatially-varying BRDFs. The normals reveal fine-scale surface detail, allowing much richer renderings than the voxel geometry alone.