A5070335899- Protein Structure and Dynamics
- Spectroscopy and Quantum Chemical Studies
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Photochemistry and Electron Transfer Studies
- Computational Drug Discovery Methods
- Photoreceptor and optogenetics research
- Material Dynamics and Properties
- Free Radicals and Antioxidants
- RNA and protein synthesis mechanisms
- Theoretical and Computational Physics
- Mass Spectrometry Techniques and Applications
- Hemoglobin structure and function
- Advanced Thermodynamics and Statistical Mechanics
- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- ATP Synthase and ATPases Research
- Advanced Chemical Physics Studies
- Supramolecular Self-Assembly in Materials
- Surfactants and Colloidal Systems
- Molecular spectroscopy and chirality
- Chemical Synthesis and Analysis
- Electrochemical Analysis and Applications
- Enzyme Catalysis and Immobilization
- Phase Equilibria and Thermodynamics
University of L'Aquila
2016-2025
University of Rome Tor Vergata
2005-2021
Istituto Nanoscienze
2021
Heidelberg University
2006-2010
Oak Ridge National Laboratory
2008-2009
University of Tennessee at Knoxville
2008
Sapienza University of Rome
2003-2007
Heidelberg University
2007
We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by compound databases into representative protein binding-site conformations, thus taking account the dynamic properties binding sites. also describe preliminary obtained 24 systems involving eight proteins proteome SARS-CoV-2. The involves temperature replica exchange sampling, making massively parallel...
Abstract Collective coordinates, as obtained by a principal component analysis of atomic fluctuations, are commonly used to predict low‐dimensional subspace in which essential protein motion is expected take place. The definition such an allows characterize functional, and folding, motion, provide insight into the (free) energy landscape, enhance conformational sampling molecular dynamics simulations. Here, we overview on topic, giving particular attention some methodological aspects,...
There is a gap between kinetic experiment and simulation in their views of the dynamics complex biomolecular systems. Whereas experiments typically reveal only few readily discernible exponential relaxations, simulations often indicate multistate behavior. Here, theoretical framework presented that reconciles these two approaches. The central concept “dynamical fingerprints” which contain peaks at time scales dynamical processes involved with amplitudes determined by experimental observable....
Some years ago we developed a theoretical-computational hybrid quantum/classical methodology, the Perturbed Matrix Method (PMM), to be used in conjunction with molecular dynamics simulations for investigation of chemical processes complex systems, that proved valuable tool simulation relevant experimental observables, e.g., spectroscopic signals, reduction potentials, kinetic constants. In typical PMM calculations quantum sub-part system, centre, is embedded into an external perturbing field...
The main protease (M
Photoenzymes are a rare class of biocatalysts that use light to facilitate chemical reactions. Many these catalysts utilize flavin cofactor absorb light, suggesting other flavoproteins might have latent photochemical functions. Lactate monooxygenase is flavin-dependent oxidoreductase previously reported mediate the photodecarboxylation carboxylates afford alkylated adducts. While this reaction holds potential synthetic value, mechanism and utility process unknown. Here, we combine...
Photosystem-II (PSII) is a multi-subunit protein complex that harvests sunlight to perform oxygenic photosynthesis. Initial light-activated charge separation takes place at reaction centre consisting of four chlorophylls and two pheophytins. Understanding the processes following light excitation remains elusive due spectral congestion, ultrafast nature, multi-component behaviour charge-separation process. Here, using advanced computational multiscale approaches which take into account...
Dynamic protein–solvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring light unexpected events even extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access heme...
Photosensitive proteins embedded in the cell membrane (about 5 nm thickness) act as photoactivated proton pumps, ion gates, enzymes, or more generally, initiators of stimuli for activity. They are composed a protein backbone and covalently bound cofactor (e.g. retinal chromophore bacteriorhodopsin (BR), channel rhodopsin, other opsins). The light-induced conformational changes both at basis physiological functions photosensitive proteins. Despite dramatic development microscopy techniques,...
Inhibition of the SARS-CoV-2 main protease (Mpro) is a major focus drug discovery efforts against COVID-19. Here we report hit expansion non-covalent inhibitors Mpro. Starting from recently discovered scaffold (The COVID Moonshot Consortium. Open Science Discovery Oral Non-Covalent Main Protease Inhibitor Therapeutics. bioRxiv 2020.10.29.339317) represented by an isoquinoline series, searched database over billion compounds using cheminformatics molecular fingerprinting approach. We...
Abstract Understanding the conformational transitions that trigger aggregation and amyloidogenesis of otherwise soluble peptides at atomic resolution is fundamental relevance for design effective therapeutic agents against amyloid‐related disorders. In present study transition from ideal α‐helical to β‐hairpin conformations revealed by long timescale molecular dynamics simulations in explicit water solvent, two well‐known amyloidogenic peptides: H1 peptide prion protein Aβ(12–28) fragment...
Recent work has shown that the nature of hydration pure hydrophobic surfaces changes with length scale considered: water hydrogen-bonding networks adapt to small exposed species, hydrating or “wetting” them at relatively high densities, whereas larger areas are “dewetted” [Chandler D (2005), Nature 29:640–647]. Here we determine whether this effect is also present in peptides by examining folding a β-hairpin (the 14-residue amyloidogenic prion protein H1 peptide), using microsecond...
Molecular dynamics simulation of oligopeptide chains reveals configurational subdiffusion at equilibrium extending from ${10}^{\ensuremath{-}12}$ to ${10}^{\ensuremath{-}8}\text{ }\text{ }\mathrm{s}$. Trap models, involving a random walk with distribution waiting times, cannot account for the subdiffusion, which is found rather arise fractal-like structure accessible configuration space.
Characterization of the length dependence end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding early steps protein folding. Here, poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For containing more than 10 peptide bonds loop-closing rate constants on 20–100 nanosecond time range exhibit a power-law dependence. However, this scaling breaks down for shorter peptides,...
Thermodynamic and dynamic properties of iso-1-cytochrome c covalently bound to a bare gold surface are here investigated by large scale atomistic simulations. The reduction potential the protein for low high concentrations is calculated showing good agreement with experimental estimates. origin dependence on concentration demonstrated stem from changing polarizability environment surrounding protein, mechanism reminiscent crowding effects. Moreover, structural analyses performed revealing...
The changes in the redox potential of Azurin upon mutation stem from effects a few key residues, including non-mutated ones, rather than being result generalized rearrangement.
The catalytic reaction in SARS-CoV-2 main protease is activated by a proton transfer (PT) from Cys145 to His41. same PT likely also required for the covalent binding of some inhibitors. Here we use multiscale computational approach investigate thermodynamics apo enzyme and complex with two potent inhibitors, N3 α-ketoamide 13b. We show that inhibitors free energy cost reach charge-separated state active-site dyad lower, inducing most significant reduction. few key sites (including specific...
Channelrhodopsin-2 is a photoactive membrane protein serving as an ion channel, gathering significant interest for its applications in optogenetics. Despite extensive investigation, several aspects of photocycle remain elusive and continue to be subjects ongoing debate. Of particular are the localization P480 intermediate within timing deprotonation glutamic acid E90, critical residue ChR2 functioning. In this study, we explore possibility early-P480 state, formed directly upon...
Cross-linking mass spectrometry (XL-MS) has become a powerful tool in structural biology for investigating protein structure, dynamics, and interactomics. However, short-range cross-links, defined as those connecting residues fewer than 20 positions apart, have traditionally been considered less informative largely overlooked, leaving significant data unexplored systematic manner. Here, we present system-wide analysis of demonstrating their intrinsic correlation with secondary structure. We...
Abstract The formation of amyloid fibrils is associated with major human diseases. Nevertheless, the molecular mechanism that directs nucleation these not fully understood. Here, we used dynamics simulations to study initial self‐assembly stages NH 2 ‐NFGAIL‐COOH peptide, core‐recognition motif type II diabetes islet polypeptide. were performed using multiple replicas monomers in explicit water, a confined box starting from random distribution peptides at T = 300 K and 340 K. At both...
Abstract The folding of the amyloidogenic H1 peptide MKHMAGAAAAGAVV taken from syrian hamster prion protein is explored in explicit aqueous solution at 300 K using long time scale all‐atom molecular dynamics simulations for a total simulation 1.1 μs. system, initially modeled as an α‐helix, preferentially adopts β‐hairpin structure and several unfolding/refolding events are observed, yielding very short average ∼200 ns. accessed by our reversibility allow to properly explore configurational...