Vedran Miletić

University of Rijeka · Department of Informatics

Flow at the molecular level induces shear-induced unfolding of single proteins and can drive their assembly, the mechanisms of which are not completely understood. To be able to analyze the role of flow on molecules, we present uniform-flow molecular dynamics simulations at atomic level. The pull module of the GRoningen MAchine for Chemical Simulat...

Mechanical perturbations are ubiquitous in living cells, and many biological functions are dependent on the mechanical response of lipid membranes. Recent force-spectroscopy studies have captured the step-wise fracture of stacks of bilayers, avoiding substrate effects. However, the effect of stacking bilayers, as well as the exact molecular mechani...

Background We use our earlier experimental studies of the catalytic mechanism of DNA methyltransferases to prepare in silico a family of novel mechanism-based inhibitors of human Dnmt1. Highly specific inhibitors of DNA methylation can be used for analysis of human epigenome and for the creation of iPS cells. Results We describe a set of adenosyl-...

Significance: The majority of the drugs which target membrane-embedded protease γ-secretase show an unusual biphasic activation–inhibition dose-response in cells, model animals, and humans. Semagacestat and avagacestat are two biphasic drugs that can facilitate cognitive decline in patients with Alzheimer’s disease. Initial mechanistic studies show...

Significance The majority of drugs that target membrane-embedded protease γ-secretase show unusual biphasic activation-inhibition dose-response in cells, model animals, and humans. Semagacestat and avagacestat are two biphasic-drugs that can facilitate cognitive decline in patients with Alzheimer’s disease. Initial mechanistic studies showed that t...

Dynamic changes in binding interactions within Dnmt1-inhibitor complex (PDB: 4DA4 [18]). Molecular dynamics simulations were used to visualize dynamic changes in binding interactions that are not readily visible in static crystal structures [30, 31]. The inhibitor and the interacting amino acids are shown in licorice, while the rest of the protein...

Formation of a covalent bond between our lead compound and the active site cysteine 1226 (prepared in VMD [41]). QM/MM simulation show how nucleophilic orbitals on the sulfur atom can come in the same plane as electrophilic orbitals on carbon 6 on the target base. Hydrogen atoms are shown in white, carbon in cyan, oxygen in red, nitrogen in blue, a...

Modifications in the linker. (DOC)

Modifications in the target base ring. (DOC)

Modifications in the adenine ring. (DOC)

Modifications in the ribose ring. (DOC)

Decrease in the inhibitor flexibility by modifications at multiple sites. (DOC)

Background: Inhibitors of DNA methylation can be used to control functional organization of human genome in basic research and regenerative medicine.Results: We describe a set of adenosyl-1-methyl-pyrimidin-2-one derivatives as novel mechanism-based suicide-inhibitors of mammalian DNA methyltransferase DNMT1. The inhibitors are designed to act as t...

Scalability is an important property of every large-scale recommender system. In order to ensure smooth user experience, recommendation algorithms should be optimized to work with large amounts of user data. This paper presents the optimization approach used in the development of the E-learning activities recommender system (ELARS). The recommendat...

Network availability is of paramount importance in optical telecommunication networks. Their rising connectivity and consequently their availability is compromised by link and node failures, usually due to physical force (e.g. digging, earthquake or fire). Single link failures can in turn cause multiple failures in case a failure hits a shared risk...

In optical networks a group of logically distinct links can unintentionally share a physical resource (e.g. a cable or a duct). Such a group, called shared risk link group (SRLG), introduces a situation where a single failure of common resource can cause multiple failures. Failure of common resource usually occurs due to physical force (e.g. diggin...

The paper presents analytical and simulation availability models for evaluation of optical node availability. Analytical models are developed for six ROADM (reconfigurable optical add and drop multiplexers) architectures. Availability/cost figures are calculated, compared and discussed. For one of ROADMs simulation model is created and Monte Carlo...

: The paper describes the design goals and methodology in creating a new model of optical telecommunication network. The model is implemented by discrete-event network simulator ns-3. The advantages of using the existing simulator core infrastructure provided by ns-3 are analyzed and compared to building own simulator from scratch, or selecting a...

The application of all-optical switching fabrics will be an important breakthrough in avoiding capacity bottleneck caused by electronic-switching in optical networks. All-optical domain of achieved network is characterised by absence of optical-electrical-optical conversions. In this paper, the-state-of-the-art of optical switching fabrics used in...