Article
Chemistry, Physical
Xiaoxiao Lu, Lulu Li, Xiaoren Zhang, Bina Fu, Xin Xu, Dong H. Zhang
Summary: A comparison of atomistic dynamics between microsolvated and unsolvated reactions can reveal the precise role of solvent molecules and provide insights into how solvation influences chemical reactions. In this study, a full-dimensional analytical potential energy surface was developed for the F-(H2O) + CH3I reaction, enabling efficient dynamics simulations at a quantitatively accurate level. The computed S(N)2 reactivity suppression ratio of the monosolvated F-(H2O) + CH3I reaction exhibits an inverted-V shape as a function of collision energy, indicating the combined dynamical effects of interaction time, steric hindrance, and collision-induced dehydration. Furthermore, analysis suggests that the steric effect of the F-(H2O) + CH3I reaction mainly arises from dragging the F- anion away from the central C atom, rather than shielding F- from C. This study highlights the potential for rigorously investigating the role of solvents in more complex reactions.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Farzad Molani, Simon Webb, Art E. Cho
Summary: We developed an effective binding free energy prediction protocol that incorporates QM/MM calculations and a mining minima approach. Our new protocol, Qcharge-VM2, showed better performance compared to classical methods and popular BFE methods. Although not as accurate as explicit water-based methods, Qcharge-VM2 is computationally less demanding, making it valuable in drug discovery campaigns.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Richa Arjariya, Gagandeep Kaur, Shantanu Sen, Sandeep Verma, Markus Lackinger, Thiruvancheril G. Gopakumar
Summary: The carboxylic acid moiety contributes to the variety of self-assembly structures on surfaces due to different H-bonding motifs. While monolayer structures featuring the common 2-fold cyclic H-bond motif have been observed, polymorphs exclusively based on the 3-fold cyclic H-bond motif have been predicted but remained elusive. This study demonstrates the formation of a superflower structure solely based on 3-fold cyclic H-bonds for a specific molecule. The observed dynamic conversion between the superflower and chicken-wire structures at the heptanoic acid-graphite interface indicates the influence of solvent on the stability of the superflower structure.
Article
Chemistry, Inorganic & Nuclear
Alessandro Nucera, Fabio Carniato, Zsolt Baranyai, Carlos Platas-Iglesias, Mauro Botta
Summary: The Fe(III)-Tiron system was investigated using a combination of experimental and theoretical methods to obtain the speciation in aqueous solution at different pH values. The relaxometric properties of [Fe(Tiron)3]9-, [Fe(Tiron)2(H2O)2]5-, and [Fe(Tiron)(H2O)4]- complexes were characterized using NMR experiments and calculations. The geometry of the Fe3+ coordination environment significantly affects the electronic relaxation, as evidenced by NMR profiles and calculations. Dissociation kinetics studies showed that the [Fe(Tiron)3]9- complex is relatively inert, while the [Fe(Tiron)2(H2O)2]5- complex is more labile.
INORGANIC CHEMISTRY
(2023)
Article
Plant Sciences
Subhadip Banerjee, Amrendra Tiwari, Amit Kar, Joydeb Chanda, Sayan Biswas, Gudrun Ulrich-Merzenich, Pulok K. Mukherjee
Summary: Lagenaria siceraria Stand. (bottle gourd) is traditionally used in Ayurvedic medicine for hypertension and obesity. This study investigated the lead compounds from bottle gourd and their mechanisms of action in obesity and hypertension. Metabolite screening, animal studies, and network pharmacology analyses were performed. The results showed that the compounds from bottle gourd improved lipid profiles in hyperlipidemic animals and acted through the insulin and ErbB signaling pathways. These findings suggest that bottle gourd could be a natural alternative for managing hyperlipidemia.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Chemistry, Physical
Matheus V. F. Ferraz, Jose C. S. Neto, Roberto D. Lins, Erico S. Teixeira
Summary: The prediction of the free energy of binding for protein-protein complexes using an Artificial Neural Network model is demonstrated in this study. The model, trained with Rosetta-calculated properties, showed improved performance compared to existing tools, with a root-mean-square error ranging from 1.67 kcal mol(-1) to 2.45 kcal mol(-1). Validation of the model using a variety of protein-protein complexes was also conducted.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Benedict W. J. Irwin, David J. Huggins
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2018)
Article
Chemistry, Medicinal
Alexander D. Wade, Lee-Ping Wang, David J. Huggins
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2018)
Article
Chemistry, Multidisciplinary
David J. Huggins, Philip C. Biggin, Marc A. Damgen, Jonathan W. Essex, Sarah A. Harris, Richard H. Henchman, Syma Khalid, Antonija Kuzmanic, Charles A. Laughton, Julien Michel, Adrian J. Mulholland, Edina Rosta, Mark S. P. Sansom, Marc W. van der Kamp
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2019)
Article
Chemistry, Medicinal
Alexander D. Wade, Andrea Rizzi, Yuanqing Wang, David J. Huggins
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Chemistry, Physical
Benedict W. J. Irwin, Sinisa Vukovic, Michael C. Payne, David J. Huggins
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Chemistry, Medicinal
Edouard Mullarky, Jiayi Xu, Anita D. Robin, David J. Huggins, Andy Jennings, Naoyoshi Noguchi, Andrea Olland, Damodharan Lakshminarasimhan, Michael Miller, Daisuke Tomita, Mayako Michino, Taojunfeng Su, Guoan Zhang, Andrew W. Stamford, Peter T. Meinke, Stacia Kargman, Lewis C. Cantley
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Chemistry, Physical
Alexander D. Wade, David J. Huggins
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2019)
Article
Multidisciplinary Sciences
Pooja Sharma, Robert Mahen, Maxim Rossmann, Jamie E. Stokes, Bryn Hardwick, David J. Huggins, Amy Emery, Dominique L. Kunciw, Marko Hyvonen, David R. Spring, Grahame J. McKenzie, Ashok R. Venkitaraman
SCIENTIFIC REPORTS
(2019)
Article
Chemistry, Multidisciplinary
David J. Huggins, Bryn S. Hardwick, Pooja Sharma, Amy Emery, Luca Laraia, Fengzhi Zhang, Ana J. Narvaez, Meredith Roberts-Thomson, Alex T. Crooks, Robert G. Boyle, Richard Boyce, David W. Walker, Natalia Mateu, Grahame J. McKenzie, David R. Spring, Ashok R. Venkitaraman
Article
Biochemical Research Methods
David J. Huggins
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2020)
Article
Chemistry, Medicinal
Alexander D. Wade, David J. Huggins
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Chemistry, Medicinal
John Ginn, Xiuju Jiang, Shan Sun, Mayako Michino, David J. Huggins, Zodwa Mbambo, Robert Jansen, Kyu Y. Rhee, Nancy Arango, Christopher D. Lima, Nigel Liverton, Toshihiro Imaeda, Rei Okamoto, Takanobu Kuroita, Kazuyoshi Aso, Andrew Stamford, Michael Foley, Peter T. Meinke, Carl Nathan, Ruslana Bryk
Summary: The development and effectiveness of novel analogs targeting the mycobacterial lipoamide dehydrogenase in inhibiting the growth of Mycobacterium tuberculosis was discussed in the article. These analogs showed improved permeability, potency, and selectivity, as well as on-target activity within the mycobacteria by increasing intrabacterial pyruvate levels. Improved potency and selectivity were achieved through distinct binding modalities between the mycobacterial and human enzymes.
ACS INFECTIOUS DISEASES
(2021)
Article
Chemistry, Physical
David J. Huggins
Summary: This paper presents an approach to alchemical binding free energies using OpenMM and evaluates the prediction accuracy using benchmark test sets. The findings highlight the effectiveness of some AMBER forcefields, particularly AMBER ff15ipq.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Wei Chen, Di Cui, Steven V. Jerome, Mayako Michino, Eelke B. Lenselink, David J. Huggins, Alexandre Beautrait, Jeremie Vendome, Robert Abel, Richard A. Friesner, Lingle Wang
Summary: In the hit identification stage of drug discovery, absolute protein-ligand binding free-energy perturbation (ABFEP) is a theoretically rigorous and accurate method that can greatly improve hit rates in virtual screening. In this work, an implementation of ABFEP method in FEP+ was described and validated using different compounds and protein receptors. The calculated binding free energies showed good correlation with experimental results and demonstrated the usefulness of ABFEP in improving hit rates in virtual screening.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Igor Maksimovic, Efrat Finkin-Groner, Yoshiyuki Fukase, Qingfei Zheng, Shan Sun, Mayako Michino, David J. Huggins, Robert W. Myers, Yael David
Summary: This study utilized the recent understanding of DJ-1 deglycation mechanism to develop a method for evaluating potential drug leads, establishing a new platform for targeting DJ-1.
RSC MEDICINAL CHEMISTRY
(2021)