A5031580685- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Estrogen and related hormone effects
- Enzyme Structure and Function
- Analytical Chemistry and Chromatography
- Monoclonal and Polyclonal Antibodies Research
- DNA and Nucleic Acid Chemistry
- Mycotoxins in Agriculture and Food
- Effects and risks of endocrine disrupting chemicals
- Synthesis and Biological Evaluation
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- Supramolecular Chemistry and Complexes
- Protein Hydrolysis and Bioactive Peptides
- Crystallography and molecular interactions
- Molecular Sensors and Ion Detection
- Free Radicals and Antioxidants
- RNA and protein synthesis mechanisms
- Hemoglobin structure and function
- thermodynamics and calorimetric analyses
- Cancer therapeutics and mechanisms
- Carcinogens and Genotoxicity Assessment
- Chemistry and Chemical Engineering
- Porphyrin and Phthalocyanine Chemistry
University of Parma
2016-2025
BD Biosciences (United States)
2017
Institute of Biostructure and Bioimaging
2009-2015
Istituto Nazionale Biostrutture e Biosistemi
2007-2013
Virginia Commonwealth University
2002-2008
University of Milan
2008
University of Pisa
1996
ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTTarget Flexibility: An Emerging Consideration in Drug Discovery and Design†Pietro Cozzini*‡§, Glen E. Kellogg*#, Francesca Spyrakis‡§, Donald J. Abraham‡, Gabriele Costantino∥, Andrew Emerson⊥, Fanelli∞, Holger Gohlke×, Leslie A. Kuhn¶, Garrett M. Morris●, Modesto Orozco◇, Thelma Pertinhez◆, Menico Rizzi∇, Christoph Sotriffer⊗View Author Information Department of General Inorganic Chemistry, University Parma, Via G.P. Usberti 17/A 43100, Italy,...
Two novel classes of cavitand-based coordination cages 7a--j and 8a--d have been synthesized via self-assembly procedures. The main factors controlling cage (CSA) identified in (i) a P--M--P angle close to 90 degrees between the chelating ligand metal precursor, (ii) Pd Pt as centers, (iii) weakly coordinated counterion, (iv) preorganization tetradentate cavitand ligand. Calorimetric measurements dynamic (1)H (19)F NMR experiments indicated that CSA is entropy driven. temperature range...
Inhibition of dipeptidyl peptidase IV (DPP-IV) may be exploited to maintain the incretin effect during postprandial phase. As a result, glycemic regulation and energy homeostasis improved. Food protein-derived peptides have been identified as natural agents capable inhibiting DPP-IV. Ile-Pro-Ile is most potent DPP-IV inhibitory peptide date. A minimum analogue sets (MAPS) approach was used study analogues Ile-Pro-Ile. The half maximal concentration (IC50) values 25 evaluated ranged from 3.9...
The prediction of the binding affinity between a protein and ligands is one most challenging issues for computational biochemistry drug discovery. While enthalpic contribution to routinely available with molecular mechanics methods, entropic more difficult estimate. We describe apply relatively simple intuitive calculation procedure estimating free energy 53 protein−ligand complexes formed by 17 proteins known three-dimensional structure characterized different active site polarity. HINT,...
Structural water molecules within protein active sites are relevant for ligand-protein recognition because they modify the site geometry and contribute to binding affinity. In this work an analysis of interactions between 23 ligands dimeric HIV-1 protease is reported. The X-ray structures these complexes show presence four types structural molecules: 301 (on symmetry axis), 313, 313bis, peripheral waters. Except 301, generally complemented with a symmetry-related set. GRID program was used...
A statistically validated protocol to identify "relevant" water molecules in protein binding sites using HINT score and a geometric descriptor termed Rank is described. In training, conservation/nonconservation was modeled for 86% of the waters. For test set, 87% waters were correctly classified (92% when crystallographic resolution ≤2.0 Å). Conserved make at least two hydrogen bonds with gain 0.6−2.0 kcal mol−1 more energy than nonconserved
The inhibition of cysteine biosynthesis in prokaryotes and protozoa has been proposed to be relevant for the development antibiotics. Haemophilus influenzae O-acetylserine sulfhydrylase (OASS), catalyzing l-cysteine formation, is inhibited by insertion C-terminal pentapeptide (MNLNI) serine acetyltransferase into active site. Four-hundred MNXXI pentapeptides were generated silico, docked OASS site using GOLD, scored with HINT. terminal P5 Ile accounts about 50% binding energy. Glu or Asp at...
In the search for xenoestrogens within food additives, we have analyzed Joint FAO-WHO expert committee database, containing 1500 compounds, using an integrated in silico and vitro approach. This analysis identified 31 potential estrogen receptor α ligands that were reduced to 13 upon applying a stringent filter based on ligand volume binding mode. Among xenoestrogens, four already known exhibit estrogenic activity, other nine assayed vitro, determining affinity biological effects. Propyl...
Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these are difficult to structurally characterize or model although the number of X-ray structures complexes expanding. One feature that has received little attention role water molecules interfacial region. Methodology A data set 4741 abstracted from 179 high-resolution (≤ 2.30 Å) crystal was analyzed with suite modeling tools based on HINT...
The bioactivity assessment of foodborne peptides is currently a research area great relevance, and, in particular, several studies are devoted to the antihypertensive effects through inhibition angiotensin I converting enzyme (ACE). In present work, straightforward workflow identify inhibitory from food matrices proposed, which involves hybrid vitro/in silico tandem approach. Parma dry-cured ham was chosen as case study. advantage using approach active sequences (in comparison experimental...
One factor that can strongly influence predicted free energy of binding is the ionization state functional groups on ligands and at site which calculations are performed. This analysis seldom performed except in very detailed computational simulations. In this work, we address issues (i) modeling complexity resulting from different states ligand protein residues involved binding, (ii) if, how, methods evaluate pH dependence inhibition constants, (iii) how to score protonation-dependent...
Abstract Background To understand the energetics of interaction between protein and DNA we analyzed 39 crystallographically characterized complexes with HINT (Hydropathic INTeractions) computational model. is an empirical free energy force field based on solvent partitioning small molecules water 1-octanol. Our previous studies protein-ligand demonstrated that predictions were significantly improved by taking into account energetic contribution form at least one hydrogen bond each...
The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, sulfhydrylase-A sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. sulfhydrylase plays a key role adaptation to host environment, defense mechanisms oxidative stress antibiotic resistance. Because mammals synthesize from methionine lack sulfhydrylase, enzyme potential target...
Estrogen Receptors (ERs) are ligand-dependent intracellular transcriptional factors involved in many diseases. ERs mediate of the effects estrogens, but also exogenous compounds able to interfere with ER, disrupting endocrine signaling. Among these xenobiotics, present food and feed make a relevant target context dietary modulation health. In this sense, urolithins, gut microbiota derived metabolites plant polyphenolic ellagitannins, may represent good candidates act as phytoestrogens that...