Review
Chemistry, Multidisciplinary
Katja-Sophia Csizi, Markus Reiher
Summary: Quantum mechanics/molecular mechanics (QM/MM) hybrid models are used to study chemical phenomena in complex molecular environments. While this approach allows for large system sizes at moderate computational costs, constructing the models manually can be tedious. Therefore, developing automated procedures for QM/MM model construction is desired. This article reviews the current state of QM/MM modeling with a focus on automation, covering MM model parametrization, QM region selection, and embedding schemes.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Bella L. Grigorenko, Igor V. Polyakov, Maria G. Khrenova, Goran Giudetti, Shirin Faraji, Anna I. Krylov, Alexander V. Nemukhin
Summary: We conducted computational modeling to investigate the reactions of the SARS-CoV-2 main protease (M-Pro) with four potential covalent inhibitors. Our results show that all four compounds form covalent adducts with the catalytic cysteine residue of M-Pro. The reaction mechanisms vary among the compounds, with different leaving groups and substitution mechanisms observed. These findings contribute to the search for efficient inhibitors of SARS-CoV-2 enzymes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Nanoscience & Nanotechnology
Nawras Abidi, Stephan N. Steinmann
Summary: Atomistic modeling of electrified interfaces is important in electrocatalysis, corrosion, electrodeposition, batteries, and related devices. The use of grand-canonical density functional theory (GCDFT) with implicit solvation models has become popular. However, the accuracy of these models for solvation effects at interfaces is not well known. Hybrid quantum mechanical/molecular mechanics (QM/MM) models have been proposed as a promising alternative. In this study, we demonstrate the implementation of electrostatic embedding in the VASP code and its application in GCDFT for studying the hydrogen evolution reaction (HER) on MoS2. Our results show that electrostatic embedding has a significant effect on polar sites, while having almost indistinguishable results compared to the implicit solvent for apolar systems.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Hao Jiang, Oskar K. G. Svensson, Lili Cao, Ulf Ryde
Summary: This study investigates possible proton transfer pathways within the FeMo cluster of nitrogenase during the conversion of N2H2 to NH3. The calculations suggest that the barriers for these reactions are reasonable if the S2B ligand remains bound to the cluster, but become prohibitively high if S2B dissociates. This indicates that reversible dissociation of S2B is unlikely during the normal reaction cycle.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Junbo Chen, Jason B. Harper, Junming Ho
Summary: This paper introduces an economical approach to improve the accuracy and convergence of quantum mechanics/ molecular mechanics models. By using quantum-level charges on molecular mechanics atoms, the accuracy and convergence of QM/MM models can be significantly improved.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Multidisciplinary
Ankita Tripathi, Kshatresh Dutta Dubey
Summary: This study demonstrates a method to enhance promiscuity, called allostery-driven promiscuity, using molecular dynamics simulations and hybrid QM/MM calculations. By studying the AEE enzyme, the authors show that a single site mutation can induce conformational changes in the capping loop, allowing recognition of different substrates for different functions.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Physical
Jose Luis Velazquez-Libera, Julio Caballero, Jans Alzate-Morales, J. Javier Ruiz-Pernia, Inaki Tunon
Summary: We conducted a computational study on the reaction mechanism of USP7 with Ubiquitin-Rhodamine 110-G substrate using a robust methodology. Our findings provide insights into the dynamic nature of USP7 enzyme-substrate complexes and describe the conformational changes observed in our simulations. The protein-protein interactions and geometric states identified in this study could be utilized for designing potent and selective inhibitors for USP7's activity.
Article
Chemistry, Physical
Toru Saito, Yu Takano
Summary: The study investigates the reaction mechanism of guanine oxidation induced by oxidation damage, revealing a transition from a diradical to a zwitterionic intermediate. The calculated activation energy matches the experimentally observed range, showing the significance of spin contamination in the process.
Article
Biochemistry & Molecular Biology
Maria G. Khrenova, Egor S. Bulavko, Fedor D. Mulashkin, Alexander Nemukhin
Summary: The results of studying the GTP hydrolysis reaction mechanism using QM/MM MD simulations show the crucial role of the catalytic glutamine side chain. Two distinct pathways, pathway-I and pathway-II, were identified, with pathway-I explaining the impact of the Glu138Gly mutation in RP2 on slowing down the hydrolysis rate, while pathway-II aligns more closely with experimental kinetic data of the wild-type Arl3-RP2 complex.
Article
Chemistry, Physical
Mingna Zheng, Yanwei Li, Qingzhu Zhang, Wenxing Wang
Summary: This study systematically investigates the convergence behavior of energy barriers and key structural and charge features with respect to the size of the QM region in the QM/MM approach. It is found that considering multiple conformations can accelerate the convergence, and a few dozen QM atoms are sufficient for convergence.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Rong-Zhen Liao, Jing-Xuan Zhang, Zhenyang Lin, Per E. M. Siegbahn
Summary: QM/MM calculations were used to investigate the reduction of acetylene to ethylene catalyzed by the DCCPCh enzyme with an [Fe8S9] double-cubane cluster. Various reaction pathways involving different oxidation states and protonation states were analyzed to find the most favorable one. The reaction proceeds via a special double-electron transfer induced proton transfer mechanism with the anti-ferromagnetically coupled [Fe8S8] cluster delivering electrons to the substrate.
JOURNAL OF CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Qiang Shao, Muya Xiong, Jiameng Li, Hangchen Hu, Haixia Su, Yechun Xu
Summary: This study investigated the proteolysis mechanism of SARS-CoV-2 PLpro and found that the C270R mutation affects the structural dynamics and catalytic function, leading to an inhibitory effect on the enzyme.
Article
Chemistry, Physical
Md Al Mamunur Rashid, Mofizur Rahman, Thamina Acter, Nizam Uddin
Summary: The controversies on the water surface were addressed using large scale quantum mechanical molecular dynamics simulations, revealing that the location and dipole orientation of ions strongly influence the thermodynamic and kinetic properties of the surface.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Phillip S. Hudson, Felix Aviat, Ruben Meana-Paneda, Luke Warrensford, Benjamin C. Pollard, Samarjeet Prasad, Michael R. Jones, H. Lee Woodcock, Bernard R. Brooks
Summary: Accurately predicting free energy differences is crucial for rational drug design. This study focuses on the computation of QM/MM binding free energies and evaluates different QM/MM correction methods in the context of the SAMPL8 Drugs of Abuse host-guest challenge.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Article
Chemistry, Physical
Carlos A. . Ramos-Guzman, J. Javier Ruiz-Pernia, Kirill Zinovjev, Inaki Tunon
Summary: Caspases are crucial enzymes involved in cell death and inflammatory processes. They are responsible for breaking a peptide bond adjacent to an aspartate residue. Poor regulation of caspase-mediated cell death and inflammation is associated with various diseases, including neurological and metabolic diseases and cancer.
Review
Biochemistry & Molecular Biology
D. Wuensch, A. Hahlbrock, S. Jung, T. Schirmeister, J. van den Boom, O. Schilling, S. K. Knauer, R. H. Stauber
Article
Biochemistry & Molecular Biology
Ines Schmidt, Gabriele Pradel, Ludmilla Sologub, Alexandra Golzmann, Che J. Ngwa, Anna Kucharski, Tanja Schirmeister, Ulrike Holzgrabe
BIOORGANIC & MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Roberta Ettari, Santo Previti, Sandro Cosconati, Santina Maiorana, Tanja Schirmeister, Silvana Grasso, Maria Zappala
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Medicinal
Bernd Kuhn, Michal Tichy, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jorg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, Francois Diederich, Jerome Hert
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Organic
Ming W. Shi, Scott G. Stewart, Alexandre N. Sobolev, Birger Dittrich, Tanja Schirmeister, Peter Luger, Malte Hesse, Yu-Sheng Chen, Peter R. Spackman, Mark A. Spackman, Simon Grabowsky
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Tanja Schirmeister, Swarna Oli, Hongmei Wu, Gerardo Della Sala, Valeria Costantino, Ean-Jeong Seo, Thomas Efferth
Article
Biochemistry & Molecular Biology
Santiago Royo, Tanja Schirmeister, Marcel Kaiser, Sascha Jung, Santiago Rodriguez, Jose Manuel Bautista, Florenci V. Gonzalez
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Philipp Fey, Roula Chartomatsidou, Werner Kiefer, Jeremy C. Mottram, Christian Kersten, Tanja Schirmeister
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Philipp Klein, Patrick Johe, Annika Wagner, Sascha Jung, Jonas Kuehlborn, Fabian Barthels, Stefan Tenzer, Ute Distler, Waldemar Waigel, Bernd Engels, Ute A. Hellmich, Till Opatz, Tanja Schirmeister
Article
Biochemistry & Molecular Biology
Philipp Klein, Fabian Barthels, Patrick Johe, Annika Wagner, Stefan Tenzer, Ute Distler, Thien Anh Le, Paul Schmid, Volker Engel, Bernd Engels, Ute A. Hellmich, Till Opatz, Tanja Schirmeister
Article
Biochemistry & Molecular Biology
Hannah Maus, Fabian Barthels, Stefan Josef Hammerschmidt, Katja Kopp, Benedikt Millies, Andrea Gellert, Alessia Ruggieri, Tanja Schirmeister
Summary: In recent years, dengue virus (DENV) and Zika virus (ZIKV) have emerged as global health issues due to climate change and increasing globalization. New allosteric inhibitors have been developed with improved efficacy and selectivity against the two viruses, showing promising potential for antiviral therapy.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ines Schmidt, Sarah Goellner, Antje Fuss, August Stich, Anna Kucharski, Tanja Schirmeister, Elena Katzowitsch, Heike Bruhn, Alexandra Miliu, R. Luise Krauth-Siegel, Ulrike Holzgrabe
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Lara Massai, Luigi Messori, Nicola Micale, Tanja Schirmeister, Louis Maes, Dolores Fregona, Maria Agostina Cinellu, Chiara Gabbiani
Article
Chemistry, Medicinal
Tanja Schirmeister, Janina Schmitz, Sascha Jung, Torsten Schmenger, R. Luise Krauth-Siegel, Michael Guetschow
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Medicinal
Maude Giroud, Jakov Ivkovic, Mara Martignoni, Marianne Fleuti, Nils Trapp, Wolfgang Haap, Andreas Kuglstatter, Jorg Benz, Bernd Kuhn, Tanja Schirmeister, Francois Diederich