A5087676999- Protein Structure and Dynamics
- Heat shock proteins research
- Computational Drug Discovery Methods
- Microbial Natural Products and Biosynthesis
- Enzyme Structure and Function
- Crystallization and Solubility Studies
- SARS-CoV-2 and COVID-19 Research
- X-ray Diffraction in Crystallography
- Polyoxometalates: Synthesis and Applications
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- ATP Synthase and ATPases Research
- Synthetic Organic Chemistry Methods
- Radical Photochemical Reactions
- RNA and protein synthesis mechanisms
- Enzyme Catalysis and Immobilization
- Membrane Separation and Gas Transport
- Cancer, Hypoxia, and Metabolism
- Supramolecular Chemistry and Complexes
- Fullerene Chemistry and Applications
- Photochromic and Fluorescence Chemistry
- Covalent Organic Framework Applications
- thermodynamics and calorimetric analyses
- Protein Degradation and Inhibitors
- Mitochondrial Function and Pathology
University of Pavia
2019-2025
University of Bristol
2018-2022
National Interuniversity Consortium of Materials Science and Technology
2022
Institut Català d'Investigació Química
2016-2017
Barcelona Institute for Science and Technology
2017
Shanghai Institute for Science of Science
2017
Institute of Science and Technology
2017
Imperial College London
2012-2014
The metal-driven self-assembly processes of a covalent polyoxometalate (POM)-based hybrid bearing remote terpyridine binding sites have been investigated. In strongly dissociating solvent, discrete metallomacrocycle, described as molecular triangle, is formed and characterized by 2D diffusion NMR spectroscopy (DOSY), small-angle X-ray scattering (SAXS), modeling. less the primary supramolecular structure, combining negatively charged POMs cationic metal linkers, further self-assemble through...
Abstract The photophysical properties of a Keggin‐type polyoxometalate (POM) covalently bounded to benzospiropyran (BSPR) unit have been investigated. These studies reveal that both closed and open forms are emissive with distinct spectral features ( λ em (closed form)=530 nm, (open form)=670 nm) the fluorescence BSPR hybrid is considerably enhanced compared parent compounds. While excitation energy reference compounds (370 close intense absorption responsible photochromic character (350...
Protein functions are dynamically regulated by allostery, which enables conformational communication even between faraway residues, and expresses itself in many forms, akin to different "languages": allosteric control pathways predominating an unperturbed protein often unintuitively reshaped whenever biochemical perturbations arise (e.g., mutations). To accurately model unbiased molecular dynamics (MD) simulations require integration with a reliable method able to, e.g., detect incipient...
Abstract Protein folding quality control in cells requires the activity of a class proteins known as molecular chaperones. Heat shock protein‐90 (Hsp90), multidomain ATP driven machine, is prime representative this family proteins. Interactions between Hsp90, its co‐chaperones, and client have been shown to be important facilitating correct activation clients. Hsp90 levels functions are elevated tumor cells. Here, we computationally predict regions on native structures clients c‐Abl, c‐Src,...
SARS-CoV-2 is a health threat with dire socioeconomical consequences. As the crucial mediator of infection, viral glycosylated spike protein (S) has attracted most attention and at center efforts to develop therapeutics diagnostics. Herein, we use an original decomposition approach identify energetically uncoupled substructures as antibody binding sites on fully S. Crucially, all that required are unbiased MD simulations; no prior knowledge properties or ad hoc parameter combinations needed....
The SARS-CoV-2 spike (S) protein is exposed on the viral surface and first point of contact between virus host. For these reasons it represents prime target for Covid-19 vaccines. In recent months, variants this have started to emerge. Their ability reduce or evade recognition by S-targeting antibodies poses a threat immunological treatments raises concerns their consequences vaccine efficacy. To develop model able predict potential impact S-protein mutations antibody binding sites, we...
Abstract Molecular chaperones, a family of proteins which Hsp90 and Hsp70 are integral members, form an essential machinery to maintain healthy proteomes by controlling the folding activation plethora substrate client proteins. This is achieved through cycles in Hsp70, regulated task‐specific co‐chaperones, process ATP become part complex network that undergoes extensive compositional conformational variations. Despite impressive advances structural knowledge, mechanisms regulate dynamics...
The modulation of protein function via designed small molecules is providing new opportunities in chemical biology and medicinal chemistry. While drugs have traditionally been developed to block enzymatic activities through active site occupation, a growing number strategies now aim control functions an allosteric fashion, allowing for the tuning target's activation or deactivation populations conformational ensembles that underlie its function. In context discovery leads, it would be very...
The size at which nonplanar isomers of neutral, pristine gold nanoclusters become energetically favored over planar ones is still debated amongst theoreticians and experimentalists. Spectroscopy confirms planarity preferred sizes up to Au7, however, starting with Au8, the uncertainty remains for larger nanoclusters. Au8 computational studies have had different outcomes: D4h "cloverleaf" isomer competes Td, C2v D2d "nugget" greatest energetic stability. We here examine 2D vs. 3D preference in...
Ketoreductase enzymes (KRs) with a high degree of regio- and stereoselectivity are useful biocatalysts for the production small, specific chiral alcohols from achiral ketones. Actinorhodin KR (actKR), part type II polyketide synthase involved in biosynthesis antibiotic actinorhodin, can also turn over small In vitro studies assessing stereocontrol actKR have found that, "reverse" direction, wild-type (WT) enzyme's mild preference S-α-tetralol is enhanced by certain mutations (e.g., P94L)...
Redox enzymes, mostly equipped with metal or organic cofactors, can vary their reactivity oxygen by orders of magnitude. Understanding how is controlled the protein milieu remains an open issue, broad implications for mechanistic enzymology and enzyme design. Here, we address this problem focusing on a widespread group flavoenzymes that oxidize phenolic compounds derived from microbial lignin degradation, using either cytochrome c as electron acceptor. A comprehensive phylogenetic analysis...
To carry out their functions in cells, proteins are required to fold into well-defined three-dimensional conformations. The stability of the folded state dictates several aspects protein life, such as evolution, interactions, and selection structures that ultimately linked activity. Sequence mutations may change profile consequently impact structure function. Here we use a simple, molecular dynamics-based energy decomposition approach map response each aminoacid sequences set five test with...
Mitochondrial chaperonin Heat Shock Protein 60 kDa (Hsp60) oversees the correct folding of client proteins in cooperation with Hsp10. Hsp60 monomers M first form 7-meric Single rings (S), which then pair into 14-meric Double (D) that accommodate clients their lumen. Recruitment 7 Hsp10 molecules per pole yields a sealed 28-meric Football-shaped complex (F). ATP hydrolysis each unit drives and F disassembly. The V72I mutation hereditary spastic paraplegia SPG13 impairs function despite being...
The gold(I) complexes [Au{S2CN(CH2CH═CH2)2}(L)] [L = PPh3, PCy3, PMe3, CN(t)Bu, IDip] are prepared from KS2CN(CH2CH═CH2)2 and [(L)AuCl]. compounds [L2(AuCl)2] (L2 dppa, dppf) yield [(L2){AuS2CN(CH2CH═CH2)2}2], while the cyclic complex [(dppm){Au2S2CN(CH2CH═CH2)2}]OTf is obtained [dppm(AuCl)2] AgOTf followed by KS2CN(CH2CH═CH2)2. compound [Au2{S2CN(CH2CH═CH2)2}2] [(tht)AuCl] (tht tetrahydrothiophene) diallyldithiocarbamate ligand. This product ring-closes with [Ru(═CHPh)Cl2(SIMes)(PCy3)] to...
NPAC is a cytokine-like nuclear factor involved in chromatin modification and regulation of gene expression. In humans, the C-terminal domain has conserved structure β-hydroxyacid dehydrogenases (β-HAD) protein superfamily, which forms stable tetrameric core scaffold for demethylase enzymes organizes multiple sites interactions. spite close structural resemblance to other β-HAD family members, human dehydrogenase lacks highly catalytic lysine, substituted by methionine. The reintroduction...
Experiment and theory delineate covalency, electrostatic association, relativistic effect contributions to polyoxometalate-alkali ion-pairs in water.
Abstract Fullerenes C 60 , 70 and 84 may be readily encaged within a hydrogen‐bonded dimeric capsule, based on two concave cyclotriveratrylene (CTV) scaffolds, each containing three self‐complementary 2‐ureido‐4‐[ 1H ]‐pyrimidinone (UPy) subunits. NMR spectroscopy circular dichroism studies, complemented by dispersion‐corrected DFT calculations, are reported with the aim of characterizing such capsule–fullerene complexes both structurally energetically. Six fullerenes considered: in...