Article
Biochemistry & Molecular Biology
Jinying Cheng, Xue Yin, Lulu Wang, Xianxian Liu, Fang Yang, Liguo Zhang, Tonggang Liu
Summary: This study investigates the molecular mechanism of species-selective targeting of fungal versus human HSP90 triggered by the compound A11. The results provide insights into the conformational changes and binding affinities of compound A11 to fungal and human HSP90 and identify key residues for favorable binding. This study has important implications for the development of selective inhibitors targeting fungal HSP90.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Computer Science, Interdisciplinary Applications
Martin Reinhardt, Helmut Grubmueller
Summary: Gradients in free energies are important in physical and biochemical systems, and predicting free energy differences accurately is crucial. The VI method, which utilizes uncorrelated sampling, provides optimal accuracy and has been implemented into the GROMACS MD software package. A variant of VI that avoids numerical instabilities has also been developed, allowing for the use of non-pairwise potential forms in the literature.
COMPUTER PHYSICS COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Oliver J. Melling, Marley L. Samways, Yunhui Ge, David L. Mobley, Jonathan W. Essex
Summary: Water molecules are crucial in biomolecular systems, especially at protein-ligand interfaces. However, simulating such systems is challenging due to slow water exchange between protein and solvent. To overcome this, the authors combine grand canonical Monte Carlo (GCMC) with nonequilibrium candidate Monte Carlo (NCMC) to develop grand canonical nonequilibrium candidate Monte Carlo (GCNCMC). This approach improves water sampling efficiency and enables the exploration of new ligand-binding geometries mediated by water.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Physics, Fluids & Plasmas
Sara Pelargonio, Alessio Zaccone
Summary: We derive the Langevin equation with shear flow and its corresponding fluctuation-dissipation theorems from first principles. By starting from a classical Caldeira-Leggett Hamiltonian and modifying it with a term proportional to the strain-rate tensor, we obtain a generalized Langevin equation for the sheared system. Analytical computation of noise time-correlation functions reveals different regimes based on the intensity of the shear rate. In the limit of extremely weak shear rates compared to the effective vibrational temperature of the bath, the standard, simple, and Markovian form of the Langevin equation with shear flow postulated in the literature is valid. However, for higher shear rates, the (generalized) Langevin equation becomes non-Markovian and nontrivial fluctuation-dissipation theorems are derived.
Article
Chemistry, Physical
Zhaoxi Sun, Qiaole He
Summary: The combination of free energy simulations in the alchemical and configurational spaces provides a feasible route to access the thermodynamic profiles under a computationally demanding target Hamiltonian. In this work, the possibility of further accelerating the nonequilibrium free energy simulation is explored by employing unidirectional pulling and using a selection criterion. Numerical tests are performed to provide insights and guidelines for using this selection-criterion-based scheme.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Veronika Furlan, Urban Bren
Summary: This study identified curcumin, 6-gingerol, capsaicin, and resveratrol as potential PDE4D inhibitors, with curcumin exhibiting the highest inhibitory potency. It revealed different inhibitory mechanisms of these natural polyphenols on PDE4D, providing a basis for the design of novel drugs for the treatment of Alzheimer's disease.
Article
Chemistry, Physical
Anita de Ruiter, Drazen Petrov, Chris Oostenbrink
Summary: The extended TI method can be used to select curves of low curvature, improving simulation efficiency. For hydration free energy calculations, an optimal parameterization is recommended. In calculations of relative binding free energies, optimized parameterizations of the Hamiltonian can effectively lower the curvature in the bound state of the ligand.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Bojana Kocmaruk, Akshay Krishna Ammothum Kandy, Kersti Hermansson, Jolla Kullgren, Peter Broqvist
Summary: A computational protocol is developed using the self-consistent charge density functional tight-binding method to study partially reduced redox-active oxides. The protocol allows for explicit control of the oxidation states of individual Ce atoms and exploration of various meta-stable configurations. This strategy can provide insights into the interplay between size, shape, and redox activity for nanoceria and related materials.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Shaobo Zhang, Xiaolei Fan, Alpeshkumar K. Malde, Robert G. Gilbert
Summary: This study used molecular dynamics simulations and free energy calculations to predict the binding of different GBSSI mutants to amylose fragments and to predict the effects of mutations on enzyme activity. It was found that mutants with negative binding energy are more likely to have higher enzyme activity and amylose content. This research is helpful in the development of grains with improved functional properties.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Physical
Maamar Damous, Hamza Allal, Youghourta Belhocine, Soumeya Maza, Hocine Merazig
Summary: Indole and its derivatives were studied for their inhibitory behavior against copper corrosion using DFT and molecular dynamics simulations. The presence of carbonyl and carboxylic groups in the derivatives significantly affected the inhibition efficiency, with indole showing the lowest inhibition efficiency. Neutral inhibitors mainly physisorbed to the copper surface, while deprotonated inhibitors formed strong covalent Cu-N bonds through chemisorption on the Cu(111) surface.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Physics, Fluids & Plasmas
Wentao Zhu, Jian Zhang, Jun Wang, Wenfei Li, Wei Wang
Summary: A method for enhanced sampling based on the coarse-graining of conformational space is proposed in this study, which significantly improves sampling efficiency and achieves global equilibrium when local equilibrated regions cover all interested areas of the landscape. Tested on model potentials and a protein system, the method showed enhanced sampling efficiency by more than three orders of magnitude, demonstrating its ability to efficiently solve sampling problems without high temperatures or biasing potentials.
Article
Chemistry, Physical
Zhiyi Wu, Philip C. Biggin
Summary: Absolute binding free-energy calculations play a crucial role in drug design, but accuracy is of utmost importance. This study explores the most suitable approach for simulation boxes containing lipid bilayers, and introduces the Rocklin correction method for lipid bilayer systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Yunhui Ge, David F. Hahn, David L. Mobley
Summary: Relative free energy calculations are becoming critical in early pharmaceutical design, and this study compared two methods for long-range electrostatics, finding that RF simulations are more efficient and encouraging their increased use in molecular simulations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Physical
Julien Deveimy, Alain Dequidt, Patrice Malfreyt
Summary: In this study, we utilize different methodologies including thermodynamic integration (TI), free energy perturbation (FEP), and potential of mean force (PMF) to calculate the free energy of adsorption. A model system is designed to reduce the dependence on phase space sampling and pathway choice. The reliability and efficiency of these simulations are confirmed through a thermodynamic cycle, and free energy contributions related to desorption and solvent desolvation are calculated. The agreement between different calculations of adsorption free energy provides quantitative data for understanding the energy contributions in adsorption processes.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Medicinal
Christoph Oehlknecht, Sonja Katz, Christina Kroess, Bernhard Sprenger, Petra Engele, Rainer Schneider, Chris Oostenbrink
Summary: The article introduces an efficient method for calculating protein binding free energies by combining the one-step perturbation and the third-power fitting approach. Experimental in silico saturation mutagenesis confirms the method's high accuracy in predicting relative free energies of amino acid mutations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Multidisciplinary
Matteo Vanni, Marco Bellini, Silvia Borsacchi, Lucia Calucci, Maria Caporali, Stefano Caporali, Francesco d'Acapito, Marco Geppi, Andrea Giaccherini, Andrea Ienco, Gabriele Manca, Antonio Massimiliano Mio, Giuseppe Nicotra, Werner Oberhauser, Manuel Serrano-Ruiz, Martina Banchelli, Francesco Vizza, Maurizio Peruzzini
Summary: This study provides the first complete structural characterization of 2D BP functionalized with rare discrete Pd-2 units, revealing the existence of interlayer Pd-Pd units and an increase in catalytic activity for the hydrogen evolution reaction. Multiple techniques were utilized to study the morphology of Pd-2/BP nanosheets and to uncover the coordination of Pd-2 units to phosphorus atoms in 2D BP. The presence of Pd-2 units was found to enhance the activity of Pd-2/BP as a catalyst for HER in acidic medium.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemical Research Methods
Marina Macchiagodena, Marco Pagliai, Piero Procacci
Summary: The study examined the non-covalent interaction between PF-07321332 and the SARS-CoV-2 main protease using computational methods. It found that the binding is likely to be stronger when the catalytic dyad is in a neutral state.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Biochemistry & Molecular Biology
Michela Lupi, Martina Onori, Stefano Menichetti, Sergio Abbate, Giovanna Longhi, Caterina Viglianisi
Summary: In this study, an efficient chemical resolution method was developed for the separation of racemic hydroxy substituted dithia-aza[4]helicenes. Enantiopure acids were used as resolving agents, leading to better diastereomeric separation. Highly optically pure products were obtained through subsequent manipulations.
Article
Chemistry, Physical
Piero Procacci, Guido Guarnieri
Summary: In this paper, blind predictions for the binding of WP6 with ammonium/diammonium cationic guests in the ninth challenge of SAMPL are presented. The binding free energies were calculated using a virtual double system single box approach and compared with previous submissions. The results show acceptable performance with higher accuracy than previous challenges, indicating the reliability of nonequilibrium approaches for binding free energy calculations.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Piero Procacci
Summary: In the field of drug design, a dual topology alchemical approach for calculating binding free energy between different compounds is proposed. This method overcomes the limitations of traditional single topology methods and has been validated in various test scenarios. It is specifically designed for high-performance computing facilities and can be easily implemented in popular simulation software.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Medicine, General & Internal
Roberta Cascella, Martina Banchelli, Seyyed Abolghasem Ghadami, Diletta Ami, Maria Cristina Gagliani, Alessandra Bigi, Tommaso Staderini, Davide Tampellini, Katia Cortese, Cristina Cecchi, Antonino Natalello, Hadi Adibi, Paolo Matteini, Fabrizio Chiti
Summary: This study investigated the morphological, structural, and tinctorial properties of TAR DNA-binding protein 43 (TDP-43) inclusions in neuroblastoma x spinal cord 34 (NSC-34) cells. The results showed that TDP-43 inclusions did not exhibit amyloid properties and lacked cross-beta structure and fibrillar morphology. These findings suggest that TDP-43 has a low propensity to form amyloid fibrils and instead forms other types of inclusions.
ANNALS OF MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Marina Macchiagodena, Marco Pagliai, Piero Procacci
Summary: We present a step-by-step protocol and toolkit for calculating the relative dissociation free energy (RDFE) using the GROMACS molecular dynamics package. This approach, based on a novel bidirectional nonequilibrium alchemical method, accurately computes RDFE between small molecules with different volume, charge, and chemical topology. The methodology is demonstrated using the challenging SAMPL9 batch of host-guest pairs. The article is supported by an online tutorial and a public Zenodo repository.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Marina Macchiagodena, Gavino Bassu, Irene Vettori, Emiliano Fratini, Piero Procacci, Marco Pagliai
Summary: This study investigates the structural properties of 2-butanol aqueous solutions at different concentrations using both experimental and computational methods. It has been found that 2-butanol tends to form aggregates at concentrations above 1 M, which affects the structural and dynamic properties of the solvent.
JOURNAL OF PHYSICAL CHEMISTRY A
(2022)
Article
Chemistry, Applied
Michela Lupi, Omar Salmi, Caterina Viglianisi, Stefano Menichetti
Summary: This article reports the conversion of N-thiophthalimido-arylphenothiazines 2 and triarylamines 3 to dithiabridged triarylamine hetero[4]helicenes 1 using catalytic amounts of chalcogen substituted Lewis Bases and hexafluoro isopropanol as hydrogen bond donor. The procedure provides good yields under mild reaction conditions without the need for excess Lewis Acids. It also presents a preliminary study on the control of the M and P absolute stereochemistry of helicenes 1 using enantiopure sulfur containing Lewis Bases from the natural chiral pool.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Physical
Piero Procacci, Guido Guarnieri
Summary: We describe our blind prediction of the toluene-water partition coefficients in the SAMPL9 challenge. We used an efficient MD-based nonequilibrium alchemical technique relying on the GAFF2 non-polarizable force field. The prediction was optimized based on a pre-assessment comparing with known experimental data and provides valuable insights for improving the performance of the force field in drug-receptor system calculations.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Fabio Santanni, Matteo Briganti, Giulia Serrano, Enrico Salvadori, Alessandro Veneri, Chiara Batistoni, Sofia F. Russi, Stefano Menichetti, Matteo Mannini, Mario Chiesa, Lorenzo Sorace, Roberta Sessoli
Summary: Sulfur-rich molecular complexes of dithiolene-like ligands are promising candidates for molecular spin qubits due to enhanced spin coherence properties in hydrogen-free environments. In this study, the mononegative 1,3,2-dithiazole-4-thione-5-thiolate (dttt-) ligand was used as an alternative to common dinegative dithiolate ligands. The synthesis and structural characterization of Cu2+, Ni2+, and Pt2+ complexes with this ligand were reported for the first time. XPS analysis indicated that intact molecules can be deposited on surfaces by sublimation, and AF exchange interactions mediated by S center dot center dot center dot S VdW interactions were observed.
Article
Chemistry, Multidisciplinary
Niccolo Giaconi, Lorenzo Poggini, Michela Lupi, Matteo Briganti, Anil Kumar, Tapan K. K. Das, Andrea L. L. Sorrentino, Caterina Viglianisi, Stefano Menichetti, Ron Naaman, Roberta Sessoli, Matteo Mannini
Summary: This study investigates the spin selectivity properties of a monolayer of a thioalkyl derivative on a gold surface and finds that it can act as a spin filter, discriminating flowing electrons according to their spin state based on the molecules' chirality. These results demonstrate that thioalkyl derivatives are important candidates for the development of chiral spintronic devices.
Article
Chemistry, Physical
Piero Procacci
Summary: This study tested the performance of standard molecular dynamics (MD) simulations, replicates of shorter MD simulations, and Hamiltonian Replica Exchange (HREM) simulations for sampling in two macrocyclic hosts and a drug-receptor system. The results showed that enhanced sampling techniques were necessary for reliable sampling in the macrocycle with long-lived metastable states.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Analytical
Martina Banchelli, Sara Tombelli, Marella de Angelis, Cristiano D'Andrea, Cosimo Trono, Francesco Baldini, Ambra Giannetti, Paolo Matteini
Summary: This paper presents a comprehensive study on the design and implementation of a SERS biosensor for detecting the specific miRNA biomarker miRNA-183 for COPD. By utilizing a labeled molecular beacon and a specially designed MB, the biosensor achieves high sensitivity and specificity in detecting target molecules at femtomolar concentrations, and the sensor's regenerability is also demonstrated.
ANALYTICAL METHODS
(2023)
Proceedings Paper
Optics
Andrea Barucci, Cristiano D'Andrea, Edoardo Farnesi, Martina Banchelli, Chiara Amicucci, Marella De Angelis, Chiara Marzi, Roberto Pini, Byungil Hwang, Paolo Matteini
Summary: In this study, a machine learning-based approach for protein species classification using surface-enhanced Raman spectroscopy (SERS) data was proposed. Dimensionality reduction techniques and supervised/unsupervised methods were employed to quantify the similarity of SERS spectral profiles belonging to different protein species. The approach enables fast and comprehensive discrimination of proteins as well as thorough characterization of their chemo-structural differences.
2022 ITALIAN CONFERENCE ON OPTICS AND PHOTONICS (ICOP)
(2022)