Predicting Transcription Factor Specificity with All-Atom Models

The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites, rather than an ab initio approach. Here, we examine the possibility of using structure-based energy calculations that require no knowledge of bound sites but rather start with the structure of a protein-DNA complex. We study the PurR E. coli TF, and explore to which extent atomistic models of protein-DNA complexes can be used to distinguish between cognate and non-cognate DNA sites. Particular emphasis is placed on systematic evaluation of this approach by comparing its performance with bioinformatic methods, by testing it against random decoys and sites of homologous TFs. We also examine a set of experimental mutations in both DNA and the protein. Using our explicit estimates of energy, we show that the specificity for PurR is dominated by direct protein-DNA interactions, and weakly influenced by bending of DNA.Comment: 26 pages, 3 figure

Tight Bounds for Set Disjointness in the Message Passing Model

In a multiparty message-passing model of communication, there are $k$ players. Each player has a private input, and they communicate by sending messages to one another over private channels. While this model has been used extensively in distributed computing and in multiparty computation, lower bounds on communication complexity in this model and related models have been somewhat scarce. In recent work \cite{phillips12,woodruff12,woodruff13}, strong lower bounds of the form $\Omega(n \cdot k)$ were obtained for several functions in the message-passing model; however, a lower bound on the classical Set Disjointness problem remained elusive. In this paper, we prove tight lower bounds of the form $\Omega(n \cdot k)$ for the Set Disjointness problem in the message passing model. Our bounds are obtained by developing information complexity tools in the message-passing model, and then proving an information complexity lower bound for Set Disjointness. As a corollary, we show a tight lower bound for the task allocation problem \cite{DruckerKuhnOshman} via a reduction from Set Disjointness

Continuous-Time Consensus under Non-Instantaneous Reciprocity

We consider continuous-time consensus systems whose interactions satisfy a form or reciprocity that is not instantaneous, but happens over time. We show that these systems have certain desirable properties: They always converge independently of the specific interactions taking place and there exist simple conditions on the interactions for two agents to converge to the same value. This was until now only known for systems with instantaneous reciprocity. These result are of particular relevance when analyzing systems where interactions are a priori unknown, being for example endogenously determined or random. We apply our results to an instance of such systems.Comment: 12 pages, 4 figure