Simone Fulle

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RNA requires conformational dynamics to undergo its diverse functional roles. Here, a new topological network representation of RNA structures is presented that allows analyzing RNA flexibility/rigidity based on constraint counting. The method extends the FIRST approach, which identifies flexible and rigid regions in atomic detail in a single, static,(More)
The ribosome is a large ribonucleoprotein complex that carries out protein synthesis in all kingdoms of life by translating genetic information encoded in mRNA into the amino acid sequence of a protein. The nascent poly-peptides escape the peptidyl transferase center through the ribosomal exit tunnel that spans the entire large subunit. The tunnel is(More)
We report all-atom molecular dynamics and replica exchange molecular dynamics simulations on the unbound human immunodeficiency virus type-1 (HIV-1) transactivation responsive region (TAR) RNA structure and three TAR RNA structures in bound conformations of, in total, approximately 250 ns length. We compare the extent of observed conformational sampling(More)
Release of the malaria merozoite from its host erythrocyte (egress) and invasion of a fresh cell are crucial steps in the life cycle of the malaria pathogen. Subtilisin-like protease 1 (SUB1) is a parasite serine protease implicated in both processes. In the most dangerous human malarial species, Plasmodium falciparum, SUB1 has previously been shown to have(More)
PfSUB1, a subtilisin-like protease of the human malaria parasite Plasmodium falciparum, is known to play important roles during the life cycle of the parasite and has emerged as a promising antimalarial drug target. In order to provide a detailed understanding of the origin of binding determinants of PfSUB1 substrates, we performed molecular dynamics(More)
Protein kinases are involved in a variety of diseases including cancer, inflammation, and autoimmune disorders. Although the development of new kinase inhibitors is a major focus in pharmaceutical research, a large number of kinases remained so far unexplored in drug discovery projects. The selection and assessment of targets is an essential but challenging(More)
Fast and accurate identification of active compounds is essential for effective use of virtual screening workflows. Here, we have compared the ligand-ranking efficiency of the linear interaction energy (LIE) method against standard docking approaches. Using a trypsin set of 1549 compounds, we performed 12,250 molecular dynamics simulations. The LIE method(More)
The emergence of multidrug-resistant pathogens will make current antibiotics ineffective. For linezolid, a member of the novel oxazolidinone class of antibiotics, 10 nucleotide mutations in the ribosome have been described conferring resistance. Hypotheses for how these mutations affect antibiotics binding have been derived based on comparative(More)
Novel antibacterials are urgently needed to address the growing problem of bacterial resistance to conventional antibiotics. Two-component systems (TCS) are widely used by bacteria to regulate gene expression in response to various environmental stimuli and physiological stress and have been previously proposed as promising antibacterial targets. TCS(More)
BACKGROUND Annotations of the phylogenetic tree of the human kinome is an intuitive way to visualize compound profiling data, structural features of kinases or functional relationships within this important class of proteins. The increasing volume and complexity of kinase-related data underlines the need for a tool that enables complex queries pertaining to(More)