Metal binding is important for the structural and functional characterization of proteins. Previous prediction efforts have only focused on bonding state, i.e. deciding which protein residues act as metal ligands in some binding site. Identifying the geometry of metal-binding sites, i.e. deciding which residues are jointly involved in the coordination of a metal ion is a new prediction problem that has been never attempted before from protein sequence alone. In this paper, we formulate it in the framework of learning with structured outputs. Our solution relies on the fact that, from a graph theoretical perspective, metal binding has the algebraic properties of a matroid, enabling the application of greedy algorithms for learning structured outputs. On a data set of 199 non-redundant metalloproteins, we obtained precision/recall levels of 75\%/46\% correct ligand-ion assignments, which improves to 88\%/88\% in the setting where the metal binding state is known.

We develop and test new machine learning methods for the prediction of topological representations of protein structures in the form of coarse-or fine-grained contact or distance maps that are translation and rotation invariant. The methods are based on generalized input-output hidden Markov models (GIOHMMs) and generalized recursive neural networks (GRNNs). The methods are used to predict topology directly in the fine-grained case and, in the coarsegrained case, indirectly by first learning how to score candidate graphs and then using the scoring function to search the space of possible configurations. Computer simulations show that the predictors achieve state-of-the-art performance.

We develop and test new machine learning methods for the prediction of topological representations of protein structures in the form of coarse-or fine-grained contact or distance maps that are translation and rotation invariant. The methods are based on generalized input-output hidden Markov models (GIOHMMs) and generalized recursive neural networks (GRNNs). The methods are used to predict topology directly in the fine-grained case and, in the coarsegrained case, indirectly by first learning how to score candidate graphs and then using the scoring function to search the space of possible configurations. Computer simulations show that the predictors achieve state-of-the-art performance.

We develop and test new machine learning methods for the prediction oftopological representations of protein structures in the form of coarse-or fine-grained contact or distance maps that are translation androtation invariant. The methods are based on generalized input-output hidden Markov models (GIOHMMs) and generalized recursive neural networks (GRNNs). The methods are used to predict topologydirectly in the fine-grained case and, in the coarsegrained case,indirectly by first learning how to score candidate graphs and then using the scoring function to search the space of possible configurations. Computer simulations show that the predictors achievestate-of-the-art performance.

This paper studies the problem of diffusion in Markovian models, such as hidden Markov models (HMMs) and how it makes very difficult the task of learning of long-term dependencies in sequences. Using results from Markov chain theory, we show that the problem of diffusion is reduced if the transition probabilities approach 0 or 1. Under this condition, standard HMMs have very limited modeling capabilities, but input/output HMMs can still perform interesting computations.

We introduce a recurrent architecture having a modular structure and we formulate a training procedure based on the EM algorithm. The resulting model has similarities to hidden Markov models, but supports recurrent networks processing style and allows to exploit the supervised learning paradigm while using maximum likelihood estimation. 1 INTRODUCTION Learning problems involving sequentially structured data cannot be effectively dealt with static models such as feedforward networks. Recurrent networks allow to model complex dynamical systems and can store and retrieve contextual information in a flexible way. Up until the present time, research efforts of supervised learning for recurrent networks have almost exclusively focused on error minimization by gradient descent methods. Although effective for learning short term memories, practical difficulties have been reported in training recurrent neural networks to perform tasks in which the temporal contingencies present in the input/output sequences span long intervals (Bengio et al., 1994; Mozer, 1992).

We introduce a recurrent architecture having a modular structure and we formulate a training procedure based on the EM algorithm. The resulting model has similarities to hidden Markov models, but supports recurrent networks processing style and allows to exploit the supervised learning paradigm while using maximum likelihood estimation. 1 INTRODUCTION Learning problems involving sequentially structured data cannot be effectively dealt with static models such as feedforward networks. Recurrent networks allow to model complex dynamical systems and can store and retrieve contextual information in a flexible way. Up until the present time, research efforts of supervised learning for recurrent networks have almost exclusively focused on error minimization by gradient descent methods. Although effective for learning short term memories, practical difficulties have been reported in training recurrent neural networks to perform tasks in which the temporal contingencies present in the input/output sequences span long intervals (Bengio et al., 1994; Mozer, 1992).

This paper studies the problem of diffusion in Markovian models, such as hidden Markov models (HMMs) and how it makes very difficult the task of learning of long-term dependencies in sequences. Using results from Markov chain theory, we show that the problem of diffusion is reduced if the transition probabilities approach 0 or 1. Under this condition, standard HMMs have very limited modeling capabilities, but input/output HMMs can still perform interesting computations.

Learning to recognize or predict sequences using long-term context has many applications. However, practical and theoretical problems are found in training recurrent neural networks to perform tasks in which input/output dependencies span long intervals. Starting from a mathematical analysis of the problem, we consider and compare alternative algorithms and architectures on tasks for which the span of the input/output dependencies can be controlled. Results on the new algorithms show performance qualitatively superior to that obtained with backpropagation. 1 Introduction Recurrent neural networks have been considered to learn to map input sequences to output sequences. Machines that could efficiently learn such tasks would be useful for many applications involving sequence prediction, recognition or production. However, practical difficulties have been reported in training recurrent neural networks to perform tasks in which the temporal contingencies present in the input/output sequences span long intervals. In fact, we can prove that dynamical systems such as recurrent neural networks will be increasingly difficult to train with gradient descent as the duration of the dependencies to be captured increases. A mathematical analysis of the problem shows that either one of two conditions arises in such systems.

Learning to recognize or predict sequences using long-term context has many applications. However, practical and theoretical problems are found in training recurrent neural networks to perform tasks in which input/output dependencies span long intervals. Starting from a mathematical analysis of the problem, we consider and compare alternative algorithms and architectures on tasks for which the span of the input/output dependencies can be controlled. Results on the new algorithms show performance qualitatively superior to that obtained with backpropagation. 1 Introduction Recurrent neural networks have been considered to learn to map input sequences to output sequences. Machines that could efficiently learn such tasks would be useful for many applications involving sequence prediction, recognition or production. However, practical difficulties have been reported in training recurrent neural networks to perform tasks in which the temporal contingencies present in the input/output sequences span long intervals. In fact, we can prove that dynamical systems such as recurrent neural networks will be increasingly difficult to train with gradient descent as the duration of the dependencies to be captured increases. A mathematical analysis of the problem shows that either one of two conditions arises in such systems.