Article
Chemistry, Physical
Andrew C. Simmonett, Bernard R. Brooks
Summary: The PME Hessian method, a part of the particle mesh Ewald method, has various applications including normal mode analysis and crystal structure prediction. A new efficient approximation approach has been proposed for this method, making it more feasible on commodity hardware.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Physical
Igor Chollet, Louis Lagardere, Jean-Philip Piquemal
Summary: To evaluate electrostatic interactions, molecular dynamics (MD) simulations often rely on Particle Mesh Ewald (PME) algorithm or Fast Multipole Methods (FMM) approaches. However, the scalability issue of PME simulations hinders its performance on supercomputers, while FFT-free FMM techniques are not as efficient for small- to medium-size systems. ANKH, a strategy based on interpolated Ewald summations, provides an efficient and scalable solution for systems of any size, making it suitable for high performance simulations using new generation polarizable force fields towards exascale computing.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Engineering, Chemical
Yuan Yao, Jesse Capecelatro
Summary: This study presents a numerical framework for accurately computing electrically charged particles in wall-bounded flows, removing the contribution from periodic images by agnostically solving the electric Poisson equation and strategically mapping particle charges to the grid, while enforcing appropriate boundary conditions using a signed-distance levelset function.
Article
Chemistry, Physical
Jonathon G. Gray, George M. Giambasu, David A. Case, Tyler Luchko
Summary: In this study, a new periodic version of the 3D-reference interaction site model (RISM) integral equation method is presented, which can accurately describe the distributions of water and ions in periodic systems. The method outperforms the traditional flat solvent model in interpreting crystallographic data, as demonstrated by calculations on proteins, RNAs, and small molecule crystals.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Alexander J. Bryer, Juan S. Rey, Juan R. Perilla
Summary: This paper introduces SBCG2, an updated version of the neural network-based shape-based coarse graining (SBCG) approach for creating coarse-grained molecular topologies with atomistic detail. The authors demonstrate how SBCG2 can reduce the computational costs of simulating large assemblies like the HIV-1 capsid, enabling simulation on commodity hardware. Coarse-grain modeling is a valuable tool in biomolecular research for dimensionality reduction.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Jia-Jie Feng, Jia-Nan Chen, Wei Kang, Yun-Dong Wu
Summary: This study systematically investigated protein loop structure prediction using a large number of MD simulations, revealing that the recently developed RSFF2C force field performed the best in accurately predicting 12 out of 15 long loops. High-temperature MD simulations were also explored as a cost-effective alternative, with comparable results to REMD simulations observed for the RSFF2C+TIP3P force field. Enhanced sampling techniques, such as replica exchange, with the RSFF2C force field, show promise for accurate loop structure prediction.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Multidisciplinary
Yanmei Yang, Yunju Zhang, Yuanyuan Qu, Chao Zhang, Xue-Wei Liu, Mingwen Zhao, Yuguang Mu, Weifeng Li
Summary: This study used molecular dynamics simulations to analyze the energetic features of the RBD-ACE2 complex of both SARS-CoV and SARS-CoV-2, revealing that despite high structural similarity, SARS-CoV-2 has a stronger binding to the ACE2 receptor. Key residues and binding patches in the SARS-CoV-2 RBD were identified, providing valuable insights for drug development. Furthermore, mutational sites on SARS-CoV-2 were found to unexpectedly weaken the RBD-ACE2 binding, with the E484 residue identified as particularly repulsive but beneficial for binding from an energy perspective.
Article
Chemistry, Physical
Angel Pineiro, James Pipkin, Vince Antle, Rebeca Garcia-Fandino
Summary: The formation of small hybrid aggregates between excipient and drug molecules contributes to the solubilization of active principles in pharmaceutical formulations. Characterizing these entities is challenging due to their flexibility and dynamic nature, particularly in the case of cyclodextrins and inclusion complexes. Molecular dynamics simulations were used to assess the role of spontaneous aggregation in solubilizing the drug remdesivir, shedding light on the mechanism of sulphobutylether-beta-cyclodextrins in solubilization.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Multidisciplinary Sciences
Yuyong Zhou, Karen Anbro Gammeltoft, Line Abildgaard Ryberg, Long V. Pham, Helena Damtoft Tjornelund, Alekxander Binderup, Carlos Rene Duarte Hernandez, Carlota Fernandez-Antunez, Anna Offersgaard, Ulrik Fahnfe, Gunther Herbert Johannes Peters, Santseharay Ramirez, Jens Bukh, Judith Margarete Gottwein
Summary: The oral protease inhibitor nirmatrelvir is crucial for preventing severe COVID-19, but the virus can develop resistance to it. This study identified multiple mutations that confer high resistance to nirmatrelvir, some of which decrease viral replication and protease activity, but still maintain high fitness. Other naturally occurring mutations can compensate for the fitness cost and promote viral escape. Molecular dynamics simulations showed that these mutations weaken the binding between nirmatrelvir and the protease. Additionally, the polymerase inhibitor remdesivir and monoclonal antibody bebtelovimab remained effective against nirmatrelvir-resistant variants, and combining them with nirmatrelvir enhanced treatment efficacy.
Article
Chemistry, Medicinal
Maryam Ghasemitarei, Angela Privat-Maldonado, Maksudbek Yusupov, Shadi Rahnama, Annemie Bogaerts, Mohammad Reza Ejtehadi
Summary: The study explored the impact of RBD oxidation on its binding to ACE2 and GRP78, revealing that the interaction between oxidized RBD and ACE2 is strengthened while the interaction with GRP78 is only slightly increased. This suggests a potential regulatory role of RONS in the binding of the SARS-CoV-2 S-glycoprotein to host cell receptors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Mehdi Sahihi, Jordi Faraudo
Summary: The interaction between the S protein of coronaviruses and a polystyrene surface is driven by hydrophobic and pi-pi interactions. The interaction is stronger when the S protein is in the up conformation, but weaker when in the down conformation. These results suggest that SARS-CoV-2 virions may strongly adsorb over plastic surfaces without significantly affecting their infectivity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Vytautas Gapsys, Ahmet Yildirim, Matteo Aldeghi, Yuriy Khalak, David van der Spoel, Bert L. de Groot
Summary: The study shows that non-equilibrium methods converge faster and produce accurate results in calculating protein-ligand binding free energy compared to equilibrium methods. Theoretically rigorous non-equilibrium approaches can achieve accurate absolute binding free energies in a reliable and well-converged manner.
COMMUNICATIONS CHEMISTRY
(2021)
Article
Chemistry, Physical
Jia-Nan Chen, Fan Jiang, Yun-Dong Wu
Summary: The structural characterization of protein-peptide interactions is essential for understanding biological processes and designing peptide drugs. This study proposes a simple and effective method using high-temperature molecular dynamics simulations to predict the binding site and pose of peptides simultaneously, with significantly improved accuracy compared to previous docking methods.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Physical
Shuxin He, Zonglin Gu
Summary: Due to the increasing demand for freshwater, the shortage of global freshwater resources has become a serious issue. Reverse osmosis (RO) technology has the potential to obtain freshwater from seawater. However, current RO membranes have low efficiency. In this study, a RO membrane based on a novel two-dimensional nanomaterial called boridene was designed and its desalination performance was investigated using molecular dynamics simulation. The results showed that the boridene membrane has high water permeability and ideal salt rejection, surpassing commercial RO membranes in terms of water permeability.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Alessio Bartocci, Elise Dumont
Summary: Calixarenes are important molecules in supramolecular chemistry, serving as hosts for small ligands and ligands for co-crystallization of proteins. This study focuses on the association of para-sulfonato-calix[4]arenes with an antifungal protein using molecular dynamics simulations. The results confirm the presence of two main binding sites, as detected by X-ray, and the calculated binding free energy agrees well with experimental measurements. The computational protocol used here can be applied to study the supramolecular forces involved in the calixarene-assisted co-crystallization of proteins.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Letter
Ophthalmology
M. J. Schnieders, W. Goar, M. Griess, B. R. Roos, T. E. Scheetz, E. M. Stone, J. H. Fingert
Article
Chemistry, Multidisciplinary
Louis Lagardere, Luc-Henri Jolly, Filippo Lipparini, Felix Aviat, Benjamin Stamm, Zhifeng F. Jing, Matthew Harger, Hedieh Torabifard, G. Andres Cisneros, Michael J. Schnieders, Nohad Gresh, Yvon Maday, Pengyu Y. Ren, Jay W. Ponder, Jean-Philip Piquemal
Article
Genetics & Heredity
Hela Azaiez, Kevin T. Booth, Sean S. Ephraim, Bradley Crone, Elizabeth A. Black-Ziegelbein, Robert J. Marini, A. Eliot Shearer, Christina M. Sloan-Heggen, Diana Kolbe, Thomas Casavant, Michael J. Schnieders, Carla Nishimura, Terry Braun, Richard J. H. Smith
AMERICAN JOURNAL OF HUMAN GENETICS
(2018)
Article
Chemistry, Physical
Joshua A. Rackers, Zhi Wang, Chao Lu, Marie L. Laury, Louis Lagardere, Michael J. Schnieders, Jean-Philip Piquemal, Pengyu Ren, Jay W. Ponder
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2018)
Article
Biophysics
Mallory R. Tollefson, Jacob M. Litman, Guowei Qi, Claire E. O'Connell, Matthew J. Wipfler, Robert J. Marini, Hernan Bernabe, William T. A. Tollefson, Terry A. Braun, Thomas L. Casavant, Richard J. H. Smith, Michael J. Schnieders
BIOPHYSICAL JOURNAL
(2019)
Article
Ophthalmology
Erin A. Boese, Mallory R. Tollefson, Michael J. Schnieders, Benjamin W. Darbro, Wallace L. M. Alward, John H. Fingert
CURRENT EYE RESEARCH
(2020)
Article
Chemistry, Physical
Jacob Litman, Andrew C. Thiel, Michael J. Schnieders
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2019)
Article
Obstetrics & Gynecology
Jianling Bi, Kristina W. Thiel, Jacob M. Litman, Yuping Zhang, Eric J. Devor, Andreea M. Newtson, Michael J. Schnieders, Jesus Gonzalez Bosquet, Kimberly K. Leslie
CLINICAL OBSTETRICS AND GYNECOLOGY
(2020)
Article
Ophthalmology
Joshua Hagedorn, Armin Avdic, Michael J. Schnieders, Benjamin R. Roos, Young H. Kwon, Arlene V. Drack, Erin A. Boese, John H. Fingert
Article
Chemistry, Physical
Rae A. Corrigan, Guowei Qi, Andrew C. Thiel, Jack R. Lynn, Brandon D. Walker, Thomas L. Casavant, Louis Lagardere, Jean-Philip Piquemal, Jay W. Ponder, Pengyu Ren, Michael J. Schnieders
Summary: Implicit solvent offers a compelling alternative for computationally demanding protein design, folding, and ligand screening, with mean errors in electrostatic model parameters being optimized for accuracy and applicability in simulations. Validation against explicit solvent simulations enables the use of these models in folding and design applications.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Benjamin E. Hinz, Sydney G. Walker, Austin Xiong, Rose A. Gogal, Michael J. Schnieders, Lori L. Wallrath
Summary: Mutations in the LMNA gene cause laminopathies, with different amino acid substitutions leading to distinct diseases in Lamin A/C. The nature of the amino acid replacement may dictate disease severity and pathogenicity. In silico analyses suggest potential genotype-phenotype connections in laminopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Eric C. Dybeck, Andrew Thiel, Michael J. Schnieders, Frank C. Pickard, Geoffrey P. F. Wood, Joseph F. Krzyzaniak, Bruno C. Hancock
Summary: This paper evaluates the predictive ability of different models for the thermodynamic stability of hydrated crystals in drug development using molecular dynamics simulations. It finds that the polarizable AMOEBA model provides the most accurate predictions. Furthermore, it shows that no single model can predict the phase boundary between hydrated and anhydrous crystals solely based on theory, but accurate phase diagrams can be constructed by introducing a single experimentally determined coexistence point.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Genetics & Heredity
Mallory R. Tollefson, Rose A. Gogal, A. Monique Weaver, Amanda M. Schaefer, Robert J. Marini, Hela Azaiez, Diana L. Kolbe, Donghong Wang, Amy E. Weaver, Thomas L. Casavant, Terry A. Braun, Richard J. H. Smith, Michael J. Schnieders
Summary: Hearing loss is a common sensory deficit, affecting approximately 5% of the population. The genetic variants associated with deafness exhibit significant heterogeneity, requiring expertise to determine their phenotypic consequences. However, a large portion of the genetic variants in the Deafness Variation Database (DVD) remains of uncertain significance, limiting their clinical utility.
Article
Chemistry, Physical
Rae A. Corrigan, Andrew C. Thiel, Jack R. Lynn, Thomas L. Casavant, Pengyu Ren, Jay W. Ponder, Michael J. Schnieders
Summary: Computational simulation of biomolecules is important for protein design, protein-ligand binding interactions, and biomolecular folding. Implicit solvent models are attractive alternatives to explicit solvation for describing solvation effects without including solvent degrees of freedom. This study extends the parameterization of the generalized Kirkwood implicit solvent model for biomolecules and achieves accurate simulations of protein structures.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Meeting Abstract
Biophysics
Armin Avdic, Mallory R. Tollefson, Nicole Tatro, Stephen D. LuCore, Jacob M. Litman, Timothy D. Fenn, Michael J. Schnieders
BIOPHYSICAL JOURNAL
(2017)