Università della Svizzera italiana

How computational chemistry and drug delivery techniques can support the development of new anticancer drugs

Garofalo, Mariangela ; Grazioso, Giovanni ; Cavalli, Andrea ; Sgrignani, Jacopo

In: Molecules, 2020, vol. 25, no. 7, p. 22 p

The early and late development of new anticancer drugs, small molecules or peptides can be slowed down by some issues such as poor selectivity for the target or poor ADME properties. Computer-aided drug design (CADD) and target drug delivery (TDD) techniques, although apparently far from each other, are two research fields that can give a significant contribution to overcome these problems....

Università della Svizzera italiana

Oxidation state dependent conformational changes of HMGB1 regulate the formation of the CXCL12/HMGB1 heterocomplex

Fassi, Enrico M.A. ; Sgrignani, Jacopo ; D'Agostino, Gianluca ; Cecchinato, Valentina ; Garofalo, Maura ; Grazioso, Giovanni ; Uguccioni, Mariagrazia ; Cavalli, Andrea

In: Computational and structural biotechnology journal, 2019, vol. 17, p. 886-894

High-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively via the chemokine receptor CXCR4 enhancing leukocyte recruitment. Here, we used...

Università della Svizzera italiana

Metainference : a Bayesian inference method for heterogeneous systems

Bonomi, Massimiliano ; Camilloni, Carlo ; Cavalli, Andrea ; Vendruscolo, Michele

In: Science advances, 2016, vol. 2, no. 1, p. e1501177

Modeling a complex system is almost invariably a challenging task. The incorporation of experimental observations can be used to improve the quality of a model and thus to obtain better predictions about the behavior of the corresponding system. This approach, however, is affected by a variety of different errors, especially when a system simultaneously populates an ensemble of different...

Università della Svizzera italiana

Structural biology of STAT3 and its implications for anticancer therapies development

Sgrignani, Jacopo ; Garofalo, Maura ; Matkovic, Milos ; Merulla, Jessica ; Catapano, Carlo V. ; Cavalli, Andrea

In: International journal of molecular sciences, 2018, vol. 19, no. 6, p. 1591

Transcription factors are proteins able to bind DNA and induce the transcription of specific genes. Consequently, they play a pivotal role in multiple cellular pathways and are frequently over-expressed or dysregulated in cancer. Here, we will focus on a specific “signal transducer and activator of transcription” (STAT3) factor that is involved in several pathologies, including cancer....

Università della Svizzera italiana

How phosphorylation influences E1 subunit pyruvate dehydrogenase : A computational study

Sgrignani, Jacopo ; Chen, JingJing ; Alimonti, Andrea ; Cavalli, Andrea

In: Scientific reports, 2018, vol. 8, p. 14683

Pyruvate (PYR) dehydrogenase complex (PDC) is an enzymatic system that plays a crucial role in cellular metabolism as it controls the entry of carbon into the Krebs cycle. From a structural point of view, PDC is formed by three different subunits (E1, E2 and E3) capable of catalyzing the three reaction steps necessary for the full conversion of pyruvate to acetyl-CoA. Recent investigations...

Università della Svizzera italiana

Enhancing coevolution-based contact prediction by imposing structural self-consistency of the contacts

Kassem, Maher M. ; Christoffersen, Lars B. ; Cavalli, Andrea ; Lindorff-Larsen, Kresten

In: Scientific reports, 2018, vol. 8, no. 1, p. 11112

Based on the development of new algorithms and growth of sequence databases, it has recently become possible to build robust higher-order sequence models based on sets of aligned protein sequences. Such models have proven useful in de novo structure prediction, where the sequence models are used to find pairs of residues that co-vary during evolution, and hence are likely to be in spatial...

Università della Svizzera italiana

Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle

Cavalli, Andrea ; Camilloni, Carlo ; Vendruscolo, Michele

In: The journal of chemical physics, 2013, vol. 138, no. 9, p. 094112

In order to characterise the dynamics of proteins, a well-established method is to incorporate experimental parameters as replica-averaged structural restraints into molecular dynamics simulations. Here, we justify this approach in the case of interproton distance information provided by nuclear Overhauser effects by showing that it generates ensembles of conformations according to the maximum...