Article
Biochemistry & Molecular Biology
Abdul Basit, Rakesh Kumar Mishra, Pradipta Bandyopadhyay
Summary: Binding of calcium ion to calcium-binding proteins triggers various biological processes, but calculating the binding affinity remains challenging. Implicit polarization method improves agreement between calculated and experimental results, indicating further improvement is necessary for quantitative match.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Physical
Xinqiang Ding, Bin Zhang
Summary: The fast and accurate calculation of standard binding free energy is crucial for drug design. The new method DeepBAR combines deep generative models with the Bennett acceptance ratio method to achieve an order-of-magnitude improvement in efficiency compared to traditional methods. DeepBAR is exact and does not suffer from approximations for entropic contributions, making it a valuable tool for computing standard binding free energy.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
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
Thermodynamics
Yuxin Chen, Yuewen Jiang
Summary: This paper proposes an interval energy flow (IEF) method to evaluate the operating state of integrated energy systems (IESs) utilizing hydrogen as an energy conversion carrier. The IEF is transformed into minimum and maximum optimization models using steady-state energy flow and parallelogram models. An alternating iterative method based on linear optimization and deterministic energy flow is used to obtain interval solutions. A case study demonstrates the effectiveness of the proposed method and discusses the impact of correlation on interval solutions.
Article
Biochemistry & Molecular Biology
Lucas Sousa Martins, Reinaldo W. A. Goncalves, Joana J. S. Moraes, Claudio Nahum Alves, Jose Rogerio A. Silva
Summary: In this study, molecular docking, molecular dynamics simulations, and the linear interaction energy method were used to predict binding modes and free energy of KA analogs as tyrosinase inhibitors. The results showed that the docking calculations accurately predicted the binding modes, and the MD simulations followed by the LIE method reproduced the experimental binding free energies, indicating the robustness of the theoretical model. It was found that specific residues played an important role in the binding recognition of KA analogs in the catalytic site. This study provides valuable validation for the structure-based drug design of new and potent tyrosinase inhibitors.
Article
Materials Science, Multidisciplinary
Sarath Menon, Yury Lysogorskiy, Jutta Rogal, Ralf Drautz
Summary: Automated workflows for calculating Helmholtz and Gibbs free energies with their temperature and pressure dependence were devised, along with corresponding computational tools. Non-equilibrium thermodynamics and reversible scaling were employed to evaluate free energies of solid and liquid phases at different temperatures and compute free energies over a wide range of temperatures. Alchemical and upscaling free energy calculations are possible by altering chemistry and interatomic potential, with examples showcasing the accuracy and efficiency of the implementation.
PHYSICAL REVIEW MATERIALS
(2021)
Article
Optics
Yiqing Cao, Zhijuan Shen
Summary: This paper presents a fifth-order intrinsic aberration calculation method for soft x-ray and vacuum ultraviolet optical systems, and successfully validates its accuracy.
Article
Environmental Sciences
Meng Li, Jian Zhang, Hui Sun, Fuliu Gao, Chenglang Wang, Ruoge Xu, Xiaoyan Zhao, Jun Zhou
Summary: Seismic wave travel time is an important seismic attribute information, and it is significant to study an efficient and high-precision travel time calculation method that can adapt to undulating surface condition. In this paper, the Fast iterative method (FIM) is modified to a topography travel time calculation method.
FRONTIERS IN ENVIRONMENTAL SCIENCE
(2022)
Article
Chemistry, Medicinal
Jorge Enrique Hernandez Gonzalez, Alexandre Suman de Araujo
Summary: This study presents a set of strategies, termed TIRST/TIRST-H+, to calculate the relative free energies of charge-changing mutations at protein-protein interfaces. The approaches combine thermodynamic integration with pK(a) shifts prediction, and special restraints are used to keep the transformed molecules separated. The accuracy of the methods was validated on a diverse data set, and the inclusion of variable protonation states improved the predicted Delta Delta G values.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Computer Science, Interdisciplinary Applications
Wei Cai, Peimin Zhu, Guangchao Li
Summary: This paper proposes a new algorithm for FIM, which utilizes second-order and mixed-order difference schemes under the parallel computing structure. It effectively improves the calculation accuracy of traveltimes while maintaining the original computational efficiency. Improved finite difference calculation in the diagonal direction of square grids and the double-grid technique near the source are applied to further reduce overall calculation error.
COMPUTERS & GEOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Galyna P. Volynets, Olga Gudzera, Mariia O. Usenko, Oksana B. Gorbatiuk, Sergiy M. Yarmoluk, Michael A. Tukalo
Summary: This article investigates the importance of key amino acid residues in the aminoacyl-adenylate binding site of Mycobacterium tuberculosis MetRS for substrate interaction. The mutation of Glu24 and Leu293 to alanine is found to enhance the affinity for methionyl-tRNA synthetase but leads to the loss of inhibitory activity. These residues can be further studied for confirming the binding mode of inhibitors and considered in chemical optimization to overcome resistance due to mutations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Sebastian Erfort, Martin Tschoepe, Guntram Rauhut
Summary: The newly developed program for the simulation of rovibrational nonresonant Raman spectra utilizes vibrational wavefunctions from variational configuration interaction theory for an almost fully automated calculation. With efficient contraction schemes, it requires modest computational resources and can be controlled by minimal input. Benchmark calculations and predicted spectra demonstrate its capabilities for routine application to small molecules.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Lei Zheng, Yunpeng Yang, Jingxiao Bao, Liping He, Yifei Qi, John Z. H. Zhang
Summary: This study discovered novel inhibitors of CDK2 using molecular docking and physics-based binding free energy calculation method AS-IE. The decomposition of binding free energy revealed key protein-ligand interactions and provided a good example for drug design.
CHEMICAL BIOLOGY & DRUG DESIGN
(2022)
Article
Mathematics, Applied
Weiguo Gao, Yingzhou Li, Bichen Lu
Summary: A novel orthogonalization-free method, along with two specific algorithms, is proposed to address extreme eigenvalue problems. Both algorithms converge linearly at the local level, with convergence rates depending on eigengaps. Additional measures, such as momentum acceleration, exact linesearch, and column locking, are incorporated to accelerate algorithms and reduce computational costs.
JOURNAL OF SCIENTIFIC COMPUTING
(2022)
Article
Computer Science, Information Systems
Ke Miao, Yi Zhang, Handan Jing, Shuoguang Wang, Houjun Sun
Summary: In this paper, an iterative sidelobe-seeking method for calculating the sidelobe level of arbitrarily distributed planar arrays is proposed, which significantly reduces the computation time compared to the conventional method. Numerical experiments have verified the effectiveness of the proposed method, showing similar optimization results with 80% algorithm time saved in synthesizing a sparse planar array.
Article
Biochemistry & Molecular Biology
Fiona A. Hagenbeek, Jenny van Dongen, Rene Pool, Amy C. Harms, Peter J. Roetman, Vassilios Fanos, Britt J. van Keulen, Brian R. Walker, Naama Karu, Hilleke E. Hulshoff Pol, Joost Rotteveel, Martijn J. J. Finken, Robert R. J. M. Vermeiren, Cornelis Kluft, Meike Bartels, Thomas Hankemeier, Dorret Boomsma
Summary: This study investigated the role of genetic and environmental factors in urinary metabolomics data in children. The findings suggest that urinary metabolites have significant heritability, with similar estimates for amines and organic acids, and higher estimates for steroid hormones.
Article
Biotechnology & Applied Microbiology
Anna Niehues, Daniele Bizzarri, Marcel J. T. Reinders, P. Eline Slagboom, Alain J. van Gool, Erik B. van den Akker, Peter A. C. 't Hoen
Summary: Population-scale expression profiling studies provide valuable insights into biological and disease mechanisms. Missing or incomplete phenotypic information can hinder data analysis. Metabolomics-based surrogates can be used as predictors for clinical phenotypes. In this study, metabolomic surrogates were evaluated for 17 traits using expression profiling data. The results showed that metabolomic surrogates performed similarly to reported phenotypes.
Article
Biochemistry & Molecular Biology
Zoha Kamali, Jacob M. Keaton, Shaghayegh Haghjooy Javanmard, Todd L. Edwards, Harold Snieder, Ahmad Vaez
Summary: This study identified 1880 likely causal genes for blood pressure and provided new insights into the genetic regulation of blood pressure, as well as potential opportunities for clinical application.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Clinical Neurology
Fiona Hagenbeek, Nikki Hubers, Jenny van Dongen, Rene Pool, Peter Roetman, Amy Harms, Jouke-Jan Hottenga, Thomas Hankemeier, Robert Veremeiren, Meike Bartels, Sebastien Dejean, Dorret Boomsma
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Genetics & Heredity
Zhe Wang, Andrew Emmerich, Nicolas J. Pillon, Tim Moore, Daiane Hemerich, Marilyn C. Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S. Ahluwalia, Traci M. Bartz, Amy R. Bentley, Lawrence F. Bielak, Mike Chong, Audrey Y. Chu, Diane Berry, Rajkumar Dorajoo, Nicole D. Dueker, Elisa Kasbohm, Bjarke Feenstra, Mary F. Feitosa, Christian Gieger, Mariaelisa Graff, Leanne M. Hall, Toomas Haller, Fernando P. Hartwig, David A. Hillis, Ville Huikari, Nancy Heard-Costa, Christina Holzapfel, Anne U. Jackson, Asa Johansson, Anja Moltke Jorgensen, Marika A. Kaakinen, Robert Karlsson, Kathleen F. Kerr, Boram Kim, Chantal M. Koolhaas, Zoltan Kutalik, Vasiliki Lagou, Penelope A. Lind, Mattias Lorentzon, Leo-Pekka Lyytikainen, Massimo Mangino, Christoph Metzendorf, Kristine R. Monroe, Alexander Pacolet, Louis Perusse, Rene Pool, Rebecca C. Richmond, Natalia Rivera, Sebastien Robiou-Du-Pont, Katharina E. Schraut, Christina-Alexandra Schulz, Heather M. Stringham, Toshiko Tanaka, Alexander Teumer, Constance Turman, Peter J. Van der Most, Mathias Vanmunster, Frank J. A. Van Rooij, Jana V. Van Vliet-Ostaptchouk, Xiaoshuai Zhang, Jing-Hua Zhao, Wei Zhao, Zhanna Balkhiyarova, Marie N. Balslev-Harder, Sebastian E. Baumeister, John Beilby, John Blangero, Dorret Boomsma, Soren Brage, Peter S. Braund, Jennifer A. Brody, Marcel Bruinenberg, Ulf Ekelund, Ching-Ti Liu, John W. Cole, Francis S. Collins, L. Adrienne Cupples, Tonu Esko, Stefan Enroth, Jessica D. Faul, Lindsay Fernandez-Rhodes, Alison E. Fohner, Oscar H. Franco, Tessel E. Galesloot, Scott D. Gordon, Niels Grarup, Catharina A. Hartman, Gerardo Heiss, Jennie Hui, Thomas Illig, Russell Jago, Alan James, Peter K. Joshi, Taeyeong Jung, Mika Kahonen, Tuomas O. Kilpelainen, Woon-Puay Koh, Ivana Kolcic, Peter P. Kraft, Johanna Kuusisto, Lenore J. Launer, Aihua Li, Allan Linneberg, Jian'An Luan, Pedro Marques Vidal, Sarah E. Medland, Yuri Milaneschi, Arden Moscati, Bill Musk, Christopher P. Nelson, Ilja M. Nolte, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Christine Power, Olli T. Raitakari, Magi Reedik, Alex P. Reiner, Paul M. Ridker, Igor Rudan, Kathy Ryan, Mark A. Sarzynski, Laura J. Scott, Robert A. Scott, Stephen Sidney, Kristin Siggeirsdottir, Albert Smith, Jennifer A. Smith, Emily Sonestedt, Marin Strom, E. Shyong Tai, Koon K. Teo, Barbara Thorand, Anke Toenjes, Angelo Tremblay, Andre G. Uitterlinden, Jagadish Vangipurapu, Natasja Van Schoor, Uwe Volker, Gonneke Willemsen, Kayleen Williams, Quenna Wong, Huichun Xu, Kristin L. Young, Jian Min Yuan, M. Carola Zillikens, Alan B. Zonderman, Adam Ameur, Stefania Bandinelli, Joshua C. Bis, Michael Boehnke, Claude Bouchard, Daniel Chasman, George Davey Smith, Eco J. C. De Geus, Louise Deldicque, Marcus Dorr, Michele K. Evans, Luigi Ferrucci, Myriam Fornage, Caroline Fox, Theodore Garland, Vilmundur Gudnason, Ulf Gyllensten, Torben Hansen, Caroline Hayward, Bernardo L. Horta, Elina Hypponen, Marjo-Riitta Jarvelin, W. Craig Johnson, Sharon L. R. Kardia, Lambertus A. Kiemeney, Markku Laakso, Claudia Langenberg, Terho Lehtimaki, Loic Le Marchand, Patrik K. E. Magnusson, Nicholas G. Martin, Mads Melbye, Andres Metspalu, David Meyre, Kari E. North, Claes Ohlsson, Albertine J. Oldehinkel, Marju Orho-Melander, Guillaume Pare, Taesung Park, Oluf Pedersen, Brenda W. J. H. Penninx, Tune H. Pers, Ozren Polasek, Inga Prokopenko, Charles N. Rotimi, Nilesh J. Samani, Xueling Sim, Harold Snieder, Thorkild I. A. Sorensen, Tim D. Spector, Nicholas J. Timpson, Rob M. Van Dam, Nathalie Van der Velde, Cornelia M. Van Duijn, Peter Vollenweider, Henry Volzke, Trudy Voortman, Gerard Waeber, Nicholas J. Wareham, David R. Weir, Heinz-Erich Wichmann, James F. Wilson, Andrea L. Hevener, Anna Krook, Juleen R. Zierath, Martine A. Thomis, Ruth J. F. Loos, Marcel Den Hoed
Summary: Physical activity and sedentary behavior have genetic components, and this study identified 99 genetic loci associated with self-reported physical activity, leisure screen time, and sedentary behavior. Some genetic variants were found to affect muscle function and possibly protect against exercise-induced muscle damage. Mendelian randomization analyses also revealed that the beneficial effects of reducing sedentary behavior and increasing physical activity on health outcomes may be mediated or confounded by body mass index.
Article
Behavioral Sciences
Fiona A. Hagenbeek, Jenny van Dongen, Rene Pool, Peter J. Roetman, Amy C. Harms, Jouke Jan Hottenga, Cornelis Kluft, Olivier F. Colins, Catharina E. M. van Beijsterveldt, Vassilios Fanos, Erik A. Ehli, Thomas Hankemeier, Robert R. J. M. Vermeiren, Meike Bartels, Sebastien Dejean, Dorret Boomsma
Summary: This study introduces and demonstrates the potential of an integrated multi-omics approach in investigating the biology of childhood aggressive behavior. By using single- and integrative multi-omics models, the researchers identified biomarkers for subclinical aggression and studied the connections among these biomarkers. The study found strong associations between DNA methylation, amino acids, and parental non-transmitted polygenic scores with traits like ADHD, Autism Spectrum Disorder, intelligence, smoking initiation, and self-reported health. Aggression-related omics traits were also linked to known and novel risk factors such as inflammation, carcinogens, and smoking.
Article
Chemistry, Multidisciplinary
Minglong Liu, Ryoji Yoshisada, Avand Amedi, Antonius J. P. Hopstaken, Mirte N. Pascha, Cornelis A. M. de Haan, Daan P. Geerke, David A. Poole III, Seino A. K. Jongkees
Summary: Macrocyclisation is a method to stabilize the conformation of peptides, resulting in improved stability, selectivity, affinity, and cell permeability. This work presents a new approach to peptide macrocyclisation using a cyanobenzothiazole-containing amino acid. This method can be applied to peptide discovery by mRNA display and is compatible with further peptide elaboration.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Psychiatry
Nora Strom, Dirk J. A. Smit, Talisa Silzer, Conrad Iyegbe, Christie L. Burton, Rene Pool, Mathieu Lemire, James J. Crowley, Jouke-Jan Hottenga, Volen Z. Ivanov, Henrik Larsson, Paul Lichtenstein, Patrik Magnusson, Christian Ruck, Russell J. Schachar, Hei Man Wu, Sandra M. Meier, Jennifer Crosbie, Paul D. Arnold, Manuel Mattheisen, Dorret Boomsma, David Mataix-Cols, Danielle Cath
Summary: This study reveals the heritability of hoarding symptoms and identifies genetic associations with schizophrenia, autism spectrum disorder, and educational attainment. However, no significant loci were detected in the genome-wide analysis.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Psychiatry
Ashley E. Tate, Wonuola A. Akingbuwa, Robert Karlsson, Jouke-Jan Hottenga, Rene Pool, Magnus Boman, Henrik Larsson, Sebastian Lundstrom, Paul Lichtenstein, Christel M. Middeldorp, Meike Bartels, Ralf Kuja-Halkola
Summary: This study aimed to create a model that predicted if individuals will exhibit suicidal behaviour, aggressive behaviour, both, or neither in late adolescence. The model was validated using twin samples from Sweden and the Netherlands, and showed generalizability across Northern Europe. However, the model's prediction performance for suicidal behavior in the Netherlands sample was not better than chance.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Martin Stroet, Bertrand Caron, Martin S. S. Engler, Jimi van der Woning, Aude Kauffmann, Marc van Dijk, Mohammed El-Kebir, Koen M. M. Visscher, Josef Holownia, Callum Macfarlane, Brian J. J. Bennion, Svetlana Gelpi-Dominguez, Felice C. C. Lightstone, Tijs van der Storm, Daan P. P. Geerke, Alan E. E. Mark, Gunnar W. W. Klau
Summary: OFraMP is an online tool that assigns atomic interaction parameters to large molecules by matching sub-fragments within the target molecule to equivalent sub-fragments within the ATB database. It uses a novel hierarchical matching procedure and allows users to manually alter interaction parameters and automate the submission of missing substructures to the ATB. The utility of OFraMP is demonstrated using the anti-cancer agent paclitaxel and a dendrimer used in organic semiconductor devices.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2023)
Article
Biology
Ida de Vries, Danique Ammerlaan, Tatjana Heidebrecht, Patrick H. N. Celie, Daan P. Geerke, Robbie P. Joosten, Anastassis Perrakis
Summary: Base-J (β-D-glucopyranosyloxymethyluracil) is a modified DNA nucleotide that replaces 1% of thymine in kinetoplastid flagellates. The biosynthesis and maintenance of base-J depends on the base-J-binding protein 1 (JBP1) that has a thymidine hydroxylase domain and a J-DNA-binding domain (JDBD). This study presents a crystal structure of the JDBD and proposes recognition models for JDBD binding to J-DNA, which were confirmed by mutagenesis experiments. The findings provide insights into the molecular mechanism of base-J replication.
LIFE SCIENCE ALLIANCE
(2023)
Article
Genetics & Heredity
Nikki Hubers, Fiona A. A. Hagenbeek, Rene Pool, Sebastien Dejean, Amy C. C. Harms, Peter J. J. Roetman, Catharina E. M. van Beijsterveldt, Vassilios Fanos, Erik A. A. Ehli, Robert R. J. M. Vermeiren, Meike Bartels, Jouke Jan Hottenga, Thomas Hankemeier, Jenny van Dongen, Dorret I. I. Boomsma
Summary: The field of multi-omics is evolving and aims to integrate and analyze data from multiple omics levels simultaneously. In this study, genomics, epigenomics, and metabolomics data were integrated in a multi-omics framework to identify biomarkers for ADHD and explore the connections among these omics levels.
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
(2023)
Article
Mathematics, Interdisciplinary Applications
Susanne Bruins, Jouke-Jan Hottenga, Michael C. Neale, Rene Pool, Dorret I. Boomsma, Conor V. Dolan
Summary: Genotype-environment interaction refers to the moderation of genetic effects by the environment or environmental effects by genes on a phenotype. This article introduces genotype-environment interaction models and proposes a test based on the classical twin design. Simulation studies and empirical data analysis demonstrate the feasibility of this approach for detecting genotype-environment interaction, although its power depends on the heritability of the phenotype and the strength of genetic effects.
MULTIVARIATE BEHAVIORAL RESEARCH
(2023)
Article
Obstetrics & Gynecology
Hamdi Mbarek, Scott D. Gordon, David L. Duffy, Nikki Hubers, Sally Mortlock, Jeffrey J. Beck, Jouke-Jan Hottenga, Rene Pool, Conor Dolan, Ky'Era Actkins, Zachary F. Gerring, Jenny Van Dongen, Erik A. Ehli, William G. Iacono, Matt Mcgue, Daniel Chasman, C. Scott Gallagher, Samantha L. P. Schilit, Cynthia C. Morton, Guillaume Pare, Gonneke Willemsen, David C. Whiteman, Catherine M. Olsen, Catherine Derom, Robert Vlietinck, Daniel Gudbjartsson, Lisa Cannon-Albright, Eva Krapohl, Robert Plomin, Patrik K. E. Magnusson, Nancy L. Pedersen, Pirro Hysi, Massimo Mangino, Timothy D. Spector, Teemu Palviainen, Yuri Milaneschi, Brenda W. Penninnx, Adrian Campos, Ken K. Ong, John R. B. Perry, Cornelis B. Lambalk, Jaakko Kaprio, Isleifur Olafsson, Karine Duroure, Celine Revenu, Miguel E. Renteria, Loic Yengo, Lea Davis, Eske M. Derks, Sarah E. Medland, Hreinn Stefansson, Kari Stefansson, Filippo Del Bene, Bruno Reversade, Grant W. Montgomery, Dorret Boomsma, Nicholas G. Martin
Summary: This study identified four new loci associated with female propensity for giving birth to spontaneous dizygotic twins. The novel loci, GNRH1 and FSHR, have established roles in female reproduction, while ZFPM1 and IPO8 were not previously linked to female fertility. The study also found significant genetic correlations with multiple aspects of female reproduction and body size, suggesting important roles in human evolution.
HUMAN REPRODUCTION
(2023)
Article
Neurosciences
Camiel M. van der Laan, Steve G. A. van de Weijer, Rene Pool, Jouke-Jan Hottenga, Toos C. E. M. van Beijsterveldt, Gonneke Willemsen, Meike Bartels, Michel G. Nivard, Dorret I. Boomsma
Summary: Family members resemble each other in their propensity for aggression, with approximately 50% of the variance in aggression explained by genetic influences. This study investigated the importance of PGSs and found significant direct effects on aggression for PGSs based on early-life aggression, educational attainment, and ADHD, though the explained variance was low. Further research on other PGSs related to aggression and related phenotypes is needed to determine the generalizability of these findings to overall genetic influences on aggression.
BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE
(2023)