Article
Multidisciplinary Sciences
Leonid Pereyaslavets, Ganesh Kamath, Oleg Butin, Alexey Illarionov, Michael Olevanov, Igor Kurnikov, Serzhan Sakipov, Igor Leontyev, Ekaterina Voronina, Tyler Gannon, Grzegorz Nawrocki, Mikhail Darkhovskiy, Ilya Ivahnenko, Alexander Kostikov, Jessica Scaranto, Maria G. Kurnikova, Suvo Banik, Henry Chan, Michael G. Sternberg, Subramanian K. R. S. Sankaranarayanan, Brad Crawford, Jeffrey Potoff, Michael Levitt, Roger D. Kornberg, Boris Fain
Summary: The main goal of molecular simulation is to accurately predict experimental observables of molecular systems, as well as to devise models for arbitrary neutral organic molecules. Researchers have successfully computed the solvation free energies of a diverse set of organic compounds using a polarizable force field fitted entirely to ab initio calculations, achieving high predictive accuracy.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Haohao Fu, Haochuan Chen, Marharyta Blazhynska, Emma Goulard Coderc de Lacam, Florence Szczepaniak, Anna Pavlova, Xueguang Shao, James C. Gumbart, Francois Dehez, Benoit Roux, Wensheng Cai, Christophe Chipot
Summary: Designing a reliable computational methodology to calculate protein:ligand standard binding free energies is challenging, but utilizing a rigorous statistical mechanical framework and comprehensive software can provide accurate results.
Article
Chemistry, Physical
Johannes C. B. Dietschreit, Dennis J. J. Diestler, Andreas Hulm, Christian Ochsenfeld, Rafael Gomez-Bombarelli
Summary: In this study, we investigated the calculation of activation free energy in chemical reactions and found that the approximation of the free-energy profile can lead to large errors. By defining a new exact expression, we identified an unambiguous method for calculating the activation free energy. The results suggest that this approach has practical value in dealing with high-dimensional potential energy surfaces and selecting appropriate variables.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Medicinal
Han Liu, Haohao Fu, Christophe Chipot, Xueguang Shao, Wensheng Cai
Summary: In this study, a hybrid quantum mechanical/molecular mechanics approach was used to characterize the interaction of cations and anions, and Lennard-Jones parameters were optimized to improve the description of solvent-exposed salt-bridge interactions. The findings indicate that the new parameters enhance the structural and thermodynamic description of solvent-exposed salt-bridge interactions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Richard S. Hong, Ana V. Rojas, Rajni Miglani Bhardwaj, Lingle Wang, Alessandra Mattei, Nathan S. Abraham, Kevin P. Cusack, M. Olivia Pierce, Sayan Mondal, Nada Mehio, Shailendra Bordawekar, Philip R. Kym, Robert Abel, Ahmad Y. Sheikh
Summary: This article evaluates a physics-based approach for calculating thermodynamic solubility and compares it to other machine learning methods. The results show that this approach has good predictive and differentiating power, and highlight the importance of considering crystalline packing. Additionally, it demonstrates how computed energetics can provide insights for molecule design.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Haiyang Yang, Xueyan Li, Gang Li, Huating Huang, Wenning Yang, Xiaoquan Jiang, Muli Sen, Jingjing Liu, Yang Liu, Yanli Pan, Guopeng Wang
Summary: This study emphasizes the importance of accurate quantitative determination of affinity and binding kinetics for tight binding inhibition. Recommendations on experimental design and mathematical calculation approaches are provided to evaluate affinity and BK parameters for inhibitors against xanthine oxidase. Significant differences in results and the influence of different data analytical methods on enzyme engagement in human are discussed.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Physical
Junjie Zou, Zhipeng Li, Shuai Liu, Chunwang Peng, Dong Fang, Xiao Wan, Zhixiong Lin, Tai-Sung Lee, Daniel P. Raleigh, Mingjun Yang, Carlos Simmerling
Summary: In drug discovery, altering drug compound structures to improve binding affinity and properties is common. This study presents a new method for simulating the challenging process of "scaffold hopping", demonstrating high accuracy in modeling linker contraction or expansion.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Yuchen Yuan, Qiang Cui
Summary: Free energy differences are crucial for understanding chemical and biological processes, but direct estimation with quantum mechanics is impractical. A data-driven approach using a deep neural network and enhanced sampling simulations overcomes the challenge of poor configurational overlap between different levels of theory. This approach demonstrates high accuracy and efficiency for both gas phase and condensed phase systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Monika Michaelis, Massimo Delle Piane, Dirk Rothenstein, Carole C. Perry, Lucio Colombi Ciacchi
Summary: In this study, four challenges hindering the understanding of ZnO/biomolecule interfaces at the atomic scale were overcome. The adsorption free energies predicted showed remarkable agreement with experimental measurements, revealing the mechanism of interactions between ZnO surface and amino acids.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Esra Boz, Matthias Stein
Summary: The study utilized the CREST tool to calculate non-covalent ligand-receptor interactions and energy using the GFN2-xTB method, and blind predictions were made for the binding of 10 drug molecule ligands to the CB[8] receptor. The results demonstrate that the proposed method shows good agreement with experimental values for large molecules, showcasing the effectiveness of quantum chemistry in predicting molecular interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Haohao Fu, Haochuan Chen, Wensheng Cai, Xueguang Shao, Christophe Chipot
Summary: BFEE2 aims to automate and streamline accurate absolute binding free-energy estimation, eliminating the need for extensive human intervention. It supports a wide range of force fields, provides standardized workflows, and monitors the convergence of free-energy calculations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Physics, Multidisciplinary
Xiao-Wei Qiang, Chen Zhang, Hai-Long Dong, Fu-Jia Tian, Hang Fu, Ya-Jun Yang, Liang Dai, Xing-Hua Zhang, Zhi-Jie Tan
Summary: It has been discovered that both RNA and DNA can change their twist angles through twist-stretch coupling when stretched. The coupling is positive for RNA and negative for DNA. Magnetic tweezers experiments have shown that the coupling of RNA can be reversed from positive to negative by multivalent cations. Molecular dynamics simulations have provided a unified mechanism for the couplings of both RNA and DNA.
PHYSICAL REVIEW LETTERS
(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
Nanoscience & Nanotechnology
Xiqi Wu, Wenhao Zhang, Wenting Wang, Yuhang Chen
Summary: Magnetic force microscopy (MFM) is an important instrument for characterizing magnetic materials at the nanoscale. Calibration of the magnetic tips using reference magnetic nanoparticles is necessary to eliminate errors caused by electrostatic interactions. In this study, the electrostatic force on Fe3O4 nanoparticles is evaluated in order to determine the magnetic moment and dipole radius of the MFM tip. The combination of MFM and Kelvin probe force microscopy, along with theoretical modeling, effectively eliminates the electrostatic contribution. Numerical simulations and experiments on nickel nanoparticles demonstrate the decoupling's effectiveness.
Article
Chemistry, Medicinal
Alberto M. Dos Santos, Amanda Ruslana Santana Oliveira, Clauber H. S. da Costa, Peter W. Kenny, Carlos A. Montanari, Jaldyr de Jesus G. Varela, Jeronimo Lameira
Summary: We used hybrid quantum mechanics/molecular mechanics (QM/MM) simulations to study the covalent inhibition of cathepsin K and its reversibility. The results suggest that the nucleophilic attack by the catalytic cysteine and proton transfer from the catalytic histidine occur simultaneously. The reaction is more exergonic for alkyne-based inhibitors than for nitrile-based inhibitor odanacatib, which has reversible binding. Additionally, gas-phase energies were calculated to assess electrophilicity of warheads in cysteine protease inhibitor design.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Hematology
Emma-Ruoqi Xu, Soren von Bulow, Po-Chia Chen, Peter J. Lenting, Katra Kolsek, Camilo Aponte-Santamaria, Bernd Simon, Jaelle Foot, Tobias Obser, Reinhard Schneppenheim, Frauke Grater, Cecile V. Denis, Matthias Wilmanns, Janosch Hennig
Article
Chemistry, Physical
Jeffry Setiadi, Serdar Kuyucak
JOURNAL OF CHEMICAL PHYSICS
(2019)
Article
Biochemistry & Molecular Biology
Pravin Kumar Ankush Jagtap, Marisa Mueller, Pawel Masiewicz, Soeren von Buloew, Nele Merret Hollmann, Po-Chia Chen, Bernd Simon, Andreas W. Thomae, Peter B. Becker, Janosch Hennig
NUCLEIC ACIDS RESEARCH
(2019)
Article
Biophysics
Jeffry Setiadi, Serdar Kuyucak
BIOPHYSICAL JOURNAL
(2019)
Review
Biochemistry & Molecular Biology
Lyudmila Dimitrova-Paternoga, Pravin Kumar Ankush Jagtap, Po-Chia Chen, Janosch Hennig
Article
Chemistry, Multidisciplinary
Po-chia Chen, Pawel Masiewicz, Kathryn Perez, Janosch Hennig
Article
Hematology
Volker Huck, Po-Chia Chen, Emma-Ruoqi Xu, Alexander Tischer, Ulrike Klemm, Camilo Aponte-Santamaria, Christian Mess, Tobias Obser, Fabian Kutzki, Gesa Koenig, Cecile V. Denis, Frauke Graeter, Matthias Wilmanns, Matthew Auton, Stefan W. Schneider, Reinhard Schneppenheim, Janosch Hennig, Maria A. Brehm
Summary: This study uncovered a prothrombotic gain of function associated with a VWF variant located in the C4 domain, leading to an increase in platelet aggregate size and affecting the structural flexibility. The research highlights the uniqueness of this VWF variant and its significance for vascular health.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Multidisciplinary Sciences
Sharon L. Wong, Nikhil T. Awatade, Miro A. Astore, Katelin M. Allan, Michael J. Carnell, Iveta Slapetova, Po-chia Chen, Alexander Capraro, Laura K. Fawcett, Renee M. Whan, Renate Griffith, Chee Y. Ooi, Serdar Kuyucak, Adam Jaffe, Shafagh A. Waters
Summary: In this study, the characterization of the I37R mutation in the lasso motif of the CFTR chloride channel was conducted. It was found that the I37R-CFTR mutation results in a residual function defect that can be treated with potentiators and type III correctors. This study provides insights into CFTR channel regulation and offers a potential pathway for drug access in CF patients with ultra-rare genotypes.
Article
Biochemistry & Molecular Biology
Sharon L. Wong, Nikhil T. Awatade, Miro A. Astore, Katelin M. Allan, Michael J. Carnell, Iveta Slapetova, Po-Chia Chen, Jeffry Setiadi, Elvis Pandzic, Laura K. Fawcett, John R. Widger, Renee M. Whan, Renate Griffith, Chee Y. Ooi, Serdar Kuyucak, Adam Jaffe, Shafagh A. Waters
Summary: This study investigated the structural and functional defects of the rare CFTR mutation R352Q in cell models of the airway and gut. The mutation showed residual CFTR function, which could be restored by CFTR potentiators but not the corrector. Molecular dynamics simulations indicated a chloride conductance defect rather than a gating defect. The combination of in vitro patient-derived cell models and in silico simulations can improve predictions of modulator response and aid in CF precision medicine.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Po-Chia Chen, Fabian Kutzki, Angelika Mojzisch, Bernd Simon, Emma-Ruoqi Xu, Camilo Aponte-Santamaria, Kai Horny, Cy Jeffries, Reinhard Schneppenheim, Matthias Wilmanns, Maria A. Brehm, Frauke Graeter, Janosch Hennig
Summary: Von Willebrand disease is a bleeding disorder associated with mutations in the VWF gene. This study investigates the structure and dynamics of the C6 domain and the G2705R variant in C6, using nuclear magnetic resonance spectroscopy, molecular dynamics simulations and aggregometry. The findings show that the G2705R mutation destabilizes VWF by promoting hinging between the subdomains of C6.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Pediatrics
Katelin M. Allan, Miro A. Astore, Laura K. Fawcett, Sharon L. Wong, Po-Chia Chen, Renate Griffith, Adam Jaffe, Serdar Kuyucak, Shafagh A. Waters
Summary: Cystic Fibrosis (CF) is caused by mutations in the CFTR gene, and targeted therapies have been developed to restore the function of CFTR protein. This study demonstrated in vitro and in vivo that a combination of modulators can effectively address the folding and gating defects of CFTR.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Katelin M. Allan, Miro A. Astore, Egi Kardia, Sharon L. Wong, Laura K. Fawcett, Jessica L. Bell, Simone Visser, Po-Chia Chen, Renate Griffith, Adam Jaffe, Sheila Sivam, Orazio Vittorio, Serdar Kuyucak, Shafagh A. Waters
Summary: This study investigated the efficacy of Elexacaftor/Tezacaftor/Ivacaftor (ETI) CFTR modulator treatment in a patient with cystic fibrosis (CF) carrying the rare Q1291H-CFTR allele and the common F508del allele. The results showed that ETI treatment did not improve the symptoms in this patient, and the CFTR protein expression was defective with abnormal gene splicing. This study provides insights for personalized treatment strategies and optimizing clinical outcomes in individuals with rare CF manifestations or rare CFTR mutations.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Meeting Abstract
Biophysics
Miro A. Astore, Po-Chia Chen, Shafagh Waters, Serdar Kuyucak
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Miro A. Astore, Po-Chia Chen, Shafagh Waters, Serdar Kuyucak
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Po-Chia Chen, Maggy Hologne, Olivier Walker, Janosch Hennig
BIOPHYSICAL JOURNAL
(2020)
