Building a privacy-preserving semantic overlay for Peer-to-Peer networks

Searching a Peer-to-Peer (P2P) network without using a central index has been widely investigated but proved to be very difficult. Various strategies have been proposed, however no practical solution to date also addresses privacy concerns. By clustering peers which have similar interests, a semantic overlay provides a method for achieving scalable search. Traditionally, in order to find similar peers, a peer is required to fully expose its preferences for items or content, therefore disclosing this private information. However, in a hostile environment, such as a P2P system, a peer can not know the true identity or intentions of fellow peers. In this paper, we propose two protocols for building a semantic overlay in a privacy-preserving manner by modifying existing solutions to the Private Set Intersection (PSI) problem. Peers in our overlay compute their similarity to other peers in the encrypted domain, allowing them to find similar peers. Using homomorphic encryption, peers can carrying out computations on encrypted values, without needing to decrypt them first. We propose two protocols, one based on the inner product of vectors, the other on multivariate polynomial evaluation, which are able to compute a similarity value between two peers. Both protocols are implemented on top of an existing P2P platform and are designed for actual deployment. Using a supercomputer and a dataset extracted from a real world instance of a semantic overlay, we emulate our protocols in a network consisting of a thousand peers. Finally, we show the actual computational and bandwidth usage of the protocols as recorded during those experiments

Insight into mutation-induced activation of the luteinizing hormone receptor: Molecular simulations predict the functional behavior of engineered mutants at M398

In this study, molecular simulations have been combined with site-directed mutagenesis experiments to explore M398(2.43), a LH (lutropin) receptor (LHR) site in helix 2 susceptible to spontaneous activating mutations, and to develop a computational tool for predicting the functionality (i.e. active or nonactive) of LHR mutants.Site-directed mutagenesis experiments engineered 15 different substitutions for M389(2.43), which resulted in variable levels of constitutive activity, inversely correlated with the size of the replacing amino acid. This inverse correlation is suggested to be mediated by I460(3.46), M571(6.37), and Y623(7.53), the tyrosine of the NPxxY motif. In fact, size reduction at position 398(2.43), which is concurrent with constitutive receptor activity, releases the van der Waals interactions found in the wild-type LHR between M398(2.43) and these three amino acids, resulting in structural modifications in the proximity to the E/DRY/W motif. An increment, above a threshold value, in the solvent accessibility of the cytosolic ends of helices 3 and 6 is the main structural feature shared by the active mutants of the LHR. This feature has been successfully used for predicting the functionality of the engineered mutants at M398(2.43), proving that molecular simulations can be useful for in silico screening of LHR mutants