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
Lara A. Patel, Phuong Chau, Serena Debesai, Leah Darwin, Chris Neale
Summary: Computer-aided drug design has the potential to reduce the cost and effort in drug discovery. A new computational method called ligand-exchange Monte Carlo molecular dynamics is introduced, which combines molecular dynamics simulations and Monte Carlo-based ligand exchanges to optimize drug design. This method accurately calculates competitive binding free energies and identifies compounds with strong binding abilities.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
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
Biochemistry & Molecular Biology
Benjamin Ries, Karl Normak, R. Gregor Weiss, Salome Rieder, Emilia P. Barros, Candide Champion, Gerhard Konig, Sereina Riniker
Summary: This study presents an automated procedure for determining the parameters of the RE-EDS method, improving its robustness and usability. The performance of the method in calculating relative binding free energies is demonstrated through simulations of a series of checkpoint kinase 1 inhibitors.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(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
Chemistry, Medicinal
Moses K. J. Chung, Ryan J. Miller, Borna Novak, Zhi Wang, Jay W. Ponder
Summary: A major challenge in computational biophysics is accurately predicting interactions between molecules. Molecular dynamics (MD) simulations have gained interest as a tool to compute intermolecular binding affinities. The choice of a force field in MD, fixed point-charge or polarizable multipole, is an ongoing topic of discussion. In this study, we used the AMOEBA polarizable multipole force field and participated in host-guest challenges to assess its accuracy. The results showed excellent agreement between computational and experimental results, indicating the accuracy of the AMOEBA force field.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
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
Chemistry, Medicinal
Yishui Li, Runduo Liu, Jie Liu, Haibin Luo, Chengkun Wu, Zhe Li
Summary: This paper presents a newly implemented open source graph-based weighted cycle closure algorithm, which improves the calculation accuracy by considering different error contributions from different paths. The program also provides a new path-independent molecular error calculation method.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(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)
Review
Chemistry, Multidisciplinary
Haohao Fu, Haochuan Chen, Hong Zhang, Xueguang Shao, Wensheng Cai
Summary: This review discusses the importance of accurate estimation of protein-ligand binding free energies in drug design and biological engineering. The use of geometric restraints, such as funnel, spherical, and seven-degree-of-freedom restraints, is highlighted as an effective strategy to reduce configurational space and improve convergence rate in simulations. The theoretical backgrounds and methods for achieving accurate protein-ligand binding free-energy estimation through a combination of geometric restraints and importance-sampling or alchemical algorithms are also discussed.
ACTA CHIMICA SINICA
(2021)
Article
Chemistry, Physical
Zhiyi Wu, Philip C. Biggin
Summary: Absolute binding free-energy calculations play a crucial role in drug design, but accuracy is of utmost importance. This study explores the most suitable approach for simulation boxes containing lipid bilayers, and introduces the Rocklin correction method for lipid bilayer systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(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
Wei-Tse Hsu, Valerio Piomponi, Pascal T. Merz, Giovanni Bussi, Michael R. Shirts
Summary: Performing alchemical transformations is widely used in free energy calculations for biophysical processes. Alchemical methods can fail in certain scenarios, but using alchemical variables in metadynamics can enhance sampling and address these issues. In this study, alchemical metadynamics was validated and shown to accelerate sampling by introducing configurational collective variables. The necessary code changes have been released for general use in PLUMED 2.8.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Marharyta Blazhynska, Emma Goulard Coderc de Lacam, Haochuan Chen, Benoit Roux, Christophe Chipot
Summary: The study compared the rigorous geometrical route and the shortcut of omitting geometrical restraints in calculating standard binding free energies of protein-protein and protein-ligand complexes using atomistic molecular dynamics simulations. Results showed that simulations strictly following the geometrical route matched experimental measurements, while simulations without geometrical restraints converged poorly and yielded inconsistent results. This suggests the importance of including geometrical restraints for accurate calculations in molecular dynamics simulations.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemical Research Methods
Changjia Cai, Johannes Friedrich, Amrita Singh, M. Hossein Eybposh, Eftychios A. Pnevmatikakis, Kaspar Podgorski, Andrea Giovannucci
Summary: This paper introduces VolPy, a software framework that greatly simplifies preprocessing of new brain imaging datasets, making it more accessible to a wide audience. The software includes efficient algorithms that can accurately identify neurons and extract activity information. Voltage imaging enables monitoring neural activity at sub-millisecond and sub-cellular scale, providing unprecedented spatio-temporal resolution.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Thomas J. Paul, Harvey Kelly, Joshua Zuchniarz, Tahir Ahmed, Rajeev Prabhakar
CANADIAN JOURNAL OF CHEMISTRY
(2016)
Article
Chemistry, Multidisciplinary
E. Prabhu Raman, Sirish Kaushik Lakkaraju, Rajiah Aldrin Denny, Alexander D. MacKerell
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Michael C. Cavalier, Mohd Imran Ansari, Adam D. Pierce, Paul T. Wilder, Laura E. McKnight, E. Prabhu Raman, David B. Neau, Padmavani Bezawada, Milad J. Alasady, Thomas H. Charpentier, Kristen M. Varney, Eric A. Toth, Alexander D. MacKerell, Andrew Coop, David J. Weber
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Tingting Zhang, Gaurav Sharma, Thomas J. Paul, Zachary Hoffmann, Rajeev Prabhakar
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2017)
Article
Chemistry, Physical
Thomas J. Paul, Gerhard Schenk, Rajeev Prabhakar
JOURNAL OF PHYSICAL CHEMISTRY B
(2018)
Article
Chemistry, Physical
Thomas J. Paul, Tatjana N. Parac-Vogt, David Quinonero, Rajeev Prabhakar
JOURNAL OF PHYSICAL CHEMISTRY B
(2018)
Article
Chemistry, Multidisciplinary
Vindi M. Jayasinghe-Arachchige, Qiaoyu Hu, Gaurav Sharma, Thomas J. Paul, Marcus Lundberg, David Quinonero, Tatjana N. Parac-Vogt, Rajeev Prabhakar
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
E. Prabhu Raman
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Chemistry, Multidisciplinary
Audrey E. Tolbert, Catherine S. Ervin, Leela Ruckthong, Thomas J. Paul, Vindi M. Jayasinghe-Arachchige, Kosh P. Neupane, Jeanne A. Stuckey, Rajeev Prabhakar, Vincent L. Pecoraro
Review
Chemistry, Multidisciplinary
Qiaoyu Hu, Vindi M. Jayasinghe-Arachchige, Gaurav Sharma, Leonardo F. Serafim, Thomas J. Paul, Rajeev Prabhakar
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2020)
Article
Chemistry, Physical
Thomas J. Paul, Jonah Z. Vilseck, Ryan L. Hayes, Charles L. Brooks
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Chemistry, Physical
Gaurav Sharma, Qiaoyu Hu, Vindi M. Jayasinghe-Arachchige, Thomas J. Paul, Gerhard Schenk, Rajeev Prabhakar
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2019)
Article
Chemistry, Multidisciplinary
Hyuck Jin Lee, Kyle J. Korshavn, Younwoo Nam, Juhye Kang, Thomas J. Paul, Richard A. Kerr, Il Seung Youn, Mehmet Ozbil, Kwang S. Kim, Brandon T. Ruotolo, Rajeev Prabhakar, Ayyalusamy Ramamoorthy, Mi Hee Lim
CHEMISTRY-A EUROPEAN JOURNAL
(2017)