The Hanabi Challenge: A New Frontier for AI Research

From the early days of computing, games have been important testbeds for studying how well machines can do sophisticated decision making. In recent years, machine learning has made dramatic advances with artificial agents reaching superhuman performance in challenge domains like Go, Atari, and some variants of poker. As with their predecessors of chess, checkers, and backgammon, these game domains have driven research by providing sophisticated yet well-defined challenges for artificial intelligence practitioners. We continue this tradition by proposing the game of Hanabi as a new challenge domain with novel problems that arise from its combination of purely cooperative gameplay with two to five players and imperfect information. In particular, we argue that Hanabi elevates reasoning about the beliefs and intentions of other agents to the foreground. We believe developing novel techniques for such theory of mind reasoning will not only be crucial for success in Hanabi, but also in broader collaborative efforts, especially those with human partners. To facilitate future research, we introduce the open-source Hanabi Learning Environment, propose an experimental framework for the research community to evaluate algorithmic advances, and assess the performance of current state-of-the-art techniques.Comment: 32 pages, 5 figures, In Press (Artificial Intelligence

A minimal ligand binding pocket within a network of correlated mutations identified by multiple sequence and structural analysis of G protein coupled receptors

G protein coupled receptors (GPCRs) are seven helical transmembrane proteins that function as signal transducers. They bind ligands in their extracellular and transmembrane regions and activate cognate G proteins at their intracellular surface at the other side of the membrane. The relay of allosteric communication between the ligand binding site and the distant G protein binding site is poorly understood. In this study, GREMLIN 1, a recently developed method that identifies networks of co-evolving residues from multiple sequence alignments, was used to identify those that may be involved in communicating the activation signal across the membrane. The GREMLIN-predicted long-range interactions between amino acids were analyzed with respect to the seven GPCR structures that have been crystallized at the time this study was undertaken.GREMLIN significantly enriches the edges containing residues that are part of the ligand binding pocket, when compared to a control distribution of edges drawn from a random graph. An analysis of these edges reveals a minimal GPCR binding pocket containing four residues (T1183.33, M2075.42, Y2686.51 and A2927.39). Additionally, of the ten residues predicted to have the most long-range interactions (A1173.32, A2726.55, E1133.28, H2115.46, S186EC2, A2927.39, E1223.37, G902.57, G1143.29 and M2075.42), nine are part of the ligand binding pocket.We demonstrate the use of GREMLIN to reveal a network of statistically correlated and functionally important residues in class A GPCRs. GREMLIN identified that ligand binding pocket residues are extensively correlated with distal residues. An analysis of the GREMLIN edges across multiple structures suggests that there may be a minimal binding pocket common to the seven known GPCRs. Further, the activation of rhodopsin involves these long-range interactions between extracellular and intracellular domain residues mediated by the retinal domain

Time-Varying Gaussian Graphical Models of Molecular Dynamics Data

We introduce an algorithm for learning sparse, time-varying undirected probabilistic graphical models of Molecular Dynamics (MD) data. Our method computes a maximum a posteriori (MAP) estimate of the topology and parameters of the model (i.e., structure learning) using L1- regularization of the negative log-likelihood (aka ‘Graphical Lasso’) to ensure sparsity, and a kernel to ensure smoothly varying topology and parameters over time. The learning problem is posed as a convex optimization problem and then solved optimally using block coordinate descent. The resulting model encodes the time-varying joint distribution over all the dihedral angles in the protein. We apply our method to three separate MD simulations of the enzyme Cyclophilin A, a peptidylprolyl isomerase. Each simulation models the isomerization of a different substrate. We compare and contrast the graphical models constructed from each data set, providing insights into the differences in the dynamics experienced by the enzyme for the different substrate