Article
Biochemistry & Molecular Biology
Woo-jin Jeong, Jiyoon Bu, Philip Mickel, Yanxiao Han, Piper A. Rawding, Jianxin Wang, Hanbit Kang, Heejoo Hong, Petr Kral, Seungpyo Hong
Summary: Avidity-based SARS-CoV-2 antagonist, developed using dendrimer-peptide conjugates (DPCs), shows effective COVID-19 treatment by effectively blocking the interaction between ACE2 and SARS-CoV-2. The larger DPCs exhibit significantly enhanced binding strength compared to free peptides, and molecular dynamics simulation reveals how dendrimer-mediated multivalent binding enhances SARS-CoV-2 blockade.
Article
Chemistry, Multidisciplinary
Mert Y. Sengul, Alexander D. MacKerell
Summary: The presence of polarizability in the force field improves the stability of RNA hairpin structures and leads to variations in dipole moments and ion distribution. Molecular dynamics simulations play a crucial role in modeling biomolecular systems, and the treatment of electrostatic interactions in the force field strongly affects simulation accuracy. In this study, the impact of polarization on structural properties, dipole moment distributions, and cation interactions in RNA hairpin systems is investigated using polarizable and non-polarizable nucleic acid force fields.
JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Marine Bugnon, Mathilde Goullieux, Ute F. Rohrig, Marta A. S. Perez, Antoine Daina, Olivier Michielin, Vincent Zoete
Summary: Computer-aided drug design tools play a crucial role in supporting and accelerating the steps of drug discovery, with structure-based approaches using the three-dimensional structure of the targeted biomacromolecule as a major source of information. Generating parameters for small molecules remains challenging due to the large number of existing chemical groups. The updated version of SwissParam provides various new features, including the ability to set up covalent ligands and import molecules from different file formats or via a molecular sketcher.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Marcelo D. Poleto, Justin A. Lemkul
Summary: G-quadruplexes (GQs) are noncanonical nucleic acid structures formed by guanine-rich sequences in DNA and RNA. They play crucial roles in gene regulation and maintenance. This study used various simulation techniques to investigate the impact of ion binding on GQ dynamics and revealed subtle differences between DNA and RNA GQs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Kai Tao, Asuka A. Orr, Wen Hu, Pandeeswar Makam, Jiahao Zhang, Qiang Geng, Boxin Li, Joseph M. Jakubowski, Yancheng Wang, Phanourios Tamamis, Rusen Yang, Deqing Mei, Ehud Gazit
Summary: The coordination of biomolecules and metal ions has been studied, revealing co-crystallization with unusual interactions and significant catalytic behavior. Additionally, the bio-coordinated assemblies showed high piezoelectric properties, demonstrating potential for various applications.
JOURNAL OF MATERIALS CHEMISTRY A
(2021)
Article
Biochemistry & Molecular Biology
Yan Li, Ye Liu, Boya Yang, Guohui Li, Huiying Chu
Summary: A polarizable atomic multipole force field (FF) for the molecular dynamic simulation of cholesterol is proposed, based on the AMOEBA model. The proposed FF utilizes electronic parameters calculated from ab initio calculations to represent charge distribution, and models many-body polarization using distributed atomic polarizabilities. The feasibility of the proposed FF is validated through molecular dynamics (MD) simulations of bilayers composed of different cholesterol concentrations and comparisons with experimental values.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Carlos E. S. Bernardes
Summary: This study introduces a program called DLPGEN, which can generate input files for various MD programs such as GROMACS, CHARMM, DL_POLY, and LAMMPS. The program provides a method for preparing polarizable forcefields, and presents a new polarization scheme for simulating molecules with multiple virtual particles in one of the programs. The results show good agreement between data obtained using GROMACS, LAMMPS, and CHARMM, while DL_POLY may not be suitable for simulating molecules with multiple Drude particles.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Materials Science, Multidisciplinary
Junbo Zhou, Zhao Qin
Summary: Polyvinyl alcohol (PVA) is a water-soluble synthetic polymer used for biomedical applications and biodegradable products. However, it lacks mechanical strength and thermal stability. This study investigates the molecular structure and mechanics of hybrid PVA-collagen hydrogel. The results demonstrate that the interaction with collagen makes PVA structure more ordered and stiffer, leading to improved mechanical properties and higher thermal stability.
Article
Chemistry, Physical
Zhifeng Jing, Pengyu Ren
Summary: This article presents molecular dynamics simulations of two protein-RNA complexes using the AMOEBA polarizable force field. The refined parameters of the force field successfully reproduced accurate quantum-mechanical data of base-base and base-amino acid interactions, resulting in a more stable hydrogen-bond network at the interface. These simulations demonstrated the potential of polarizable force fields for studying protein-RNA complexes.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Medicinal
Ute F. Rohrig, Mathilde Goullieux, Marine Bugnon, Vincent Zoete
Summary: Molecular docking is a computational approach used to predict the position of a ligand in the binding site of a target molecule. The AC 2.0 docking algorithm has been improved to provide more robust sampling and flexibility. Experimental testing shows that AC 2.0 performs well in both redocking and cross-docking tasks, achieving good enrichment factors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Xiabin Chen, Xingyu Deng, Yun Zhang, Yanan Wu, Kang Yang, Qiang Li, Jiye Wang, Weixuan Yao, Junsen Tong, Tian Xie, Shurong Hou, Jianzhuang Yao
Summary: BZE, the major toxic metabolite of cocaine, was successfully degraded into inactive metabolites by a redesigned bacterial cocaine esterase. A new mutant, BZEease2, showed significantly improved catalytic efficiency in vivo, potentially useful for cocaine overdose treatment and environmental BZE clearance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Shiji Zhao, Haixin Wei, Piotr Cieplak, Yong Duan, Ray Luo
Summary: Molecular modeling at the atomic level is widely used in biological systems. However, additive force fields that rely on fixed atom-centered partial charges cannot accurately simulate polarization effects. This study presents PyRESP, a Python program that parameterizes atomic multipole moments by reproducing the ab initio electrostatic potential around molecules, catering to the needs of force field parameterizations in molecular modeling.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Review
Chemistry, Multidisciplinary
Kateryna Goloviznina, Zheng Gong, Agilio A. H. Padua
Summary: This article discusses the importance of using molecular dynamics simulation and theoretical chemistry tools to study ionic liquids and eutectic solvents, as well as the use of polarizable force fields to describe their interactions and conformations. The development of polarizable force fields is a combination of science and art, with the main challenge being how to handle the diversity in chemical structures and interactions to build a model that can represent solutions, mixtures, and material interfaces effectively.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Article
Chemistry, Physical
M. Lundborg, J. Lidmar, B. Hess
Summary: The accelerated weight histogram method is an enhanced sampling technique that efficiently explores free energy landscapes and can be used for sampling alchemical transformations, easy to use and can be combined with other reaction coordinates.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Physical
Ruihan Zhou, Marc Riera, Francesco Paesani
Summary: We introduce a data-driven many-body energy potential energy function (MB-nrg PEF) to accurately describe the energetics and structural properties of N-methylacetamide (NMA), as well as the NMA-water interactions. The results show that the MB-nrg PEF is able to accurately represent many-body effects in both gas and liquid phases, making it a promising molecular model for predictive simulations of biomolecular systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Medicinal
Yong Ai, Lucia Hwang, Alexander D. MacKerell, Ari Melnick, Fengtian Xue
Summary: BCL6 is a master regulator of germinal center formation, playing a crucial role in immune responses, and the protein-protein interaction between BCL6 and its corepressors has become a focus for cancer treatment research.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Anmol Kumar, Poonam Pandey, Payal Chatterjee, Alexander D. Jr Jr MacKerell
Summary: The Drude polarizable force field captures electronic polarization effects and is useful for simulating biomolecules and other molecules. Deep neural network models can accurately predict molecular dipole moments and polarizabilities.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Multidisciplinary
Abhishek A. Kognole, Jumin Lee, Sang-Jun Park, Sunhwan Jo, Payal Chatterjee, Justin A. Lemkul, Jing Huang, Alexander D. MacKerell, Wonpil Im
Summary: The Drude Prepper tool has been developed in CHARMM-GUI to facilitate the use of polarizable FF based on the classic Drude oscillator model. It allows for easy construction of Drude FF-based PSF and generation of input for MD simulations using various simulation packages. The stability and effectiveness of the Drude Prepper protocol and inputs have been demonstrated through validation with a variety of heterogeneous systems.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Adam T. Green, Amanda J. Pickard, Rongzhong Li, Alexander D. MacKerell, Ulrich Bierbach, Samuel S. Cho
Summary: This study uses circular dichroism spectroscopy to show the parallel topologies of two putative ribosomal G-quadruplex sequences, and validates and refines the modeled structures using molecular dynamics simulations. The results provide a structural foundation for understanding G-quadruplex functions and designing novel chemotherapeutics.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Review
Chemistry, Multidisciplinary
Himanshu Goel, Anthony Hazel, Wenbo Yu, Sunhwan Jo, Alexander D. MacKerell
Summary: SILCS utilizes molecular simulation to obtain functional group affinity patterns for drug discovery, allowing for identification of novel ligand binding pockets, prediction of protein-ligand binding affinities, and other applications in computer-aided drug design. It represents a comprehensive approach to improve drug development processes through accuracy and throughput enhancements.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Physical
Payal Chatterjee, Mert Y. Sengul, Anmol Kumar, Alexander D. MacKerell
Summary: The outcomes of computational chemistry and biology research are greatly influenced by the choice of forcefield used in molecular simulations. This study develops a deep learning-based framework for optimizing van der Waals interactions in molecular simulations. The resulting LJ parameters (interactions between atoms) are validated for their performance in reproducing condensed phase thermodynamic properties and demonstrate improved accuracy in reproducing solvent and crystal properties.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Medicinal
Asuka A. Orr, Suliman Sharif, Junmei Wang, Alexander D. MacKerell
Summary: Generalized force fields (FFs) are extensions of biomolecular FFs used for organic molecules. However, their application to arbitrary molecules requires caution to ensure their integrity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Abhishek A. Kognole, Anthony Hazel, Alexander D. MacKerell
Summary: RNA molecules can be potential drug targets in various diseases due to their dysregulated expression or misfolding. Noncoding RNAs, which account for a large part of the human genome, have complex structures and can be targeted by small molecules. The SILCS computational approach, termed SILCS-RNA, was extended to target RNA in this study and evaluated against seven RNA targets. The method provides detailed functional group affinity patterns and facilitates the identification of new potential binding sites and ligand design.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Chemistry, Physical
Wenbo Yu, David J. Weber, Alexander D. MacKerell
Summary: Covalent drug design plays a significant role in drug discovery by forming a covalent bond with targeted residues, leading to a more effective therapeutic approach. Computational methods can identify reactive residues, test potential reactivities, and predict noncovalent contributions to binding. SILCS, a functional group mapping approach, considers protein flexibility, functional group, and protein desolvation along with functional group-protein interactions. SILCS-Covalent, an integrated workflow, can qualitatively and quantitatively inform covalent drug discovery.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Yalun Yu, Richard M. Venable, Jonathan Thirman, Payal Chatterjee, Anmol Kumar, Richard W. Pastor, Benoit Roux, Alexander D. MacKerell Jr, Jeffery B. Klauda
Summary: Accurate empirical force fields of lipid molecules are crucial for molecular dynamics simulations of various lipid systems and heterogeneous systems. The polarizable Drude force field has been optimized in this study to improve its accuracy in simulating pure bilayers and membranes. By using both experimental and quantum mechanical data, the optimized force field shows good agreement with a range of experimental observables. The polarizable Drude2023 force field is anticipated to advance our understanding of electronic polarization in lipid systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Mingtian Zhao, Abhishek A. Kognole, Sunhwan Jo, Aoxiang Tao, Anthony Hazel, Alexander D. MacKerell Jr
Summary: In this study, the sampling efficiency of the GCMC method was improved by applying known cavity-bias and configurational-bias algorithms on GPU architecture. The method was parallelized using CUDA and OpenCL, resulting in simultaneous sampling of a large number of configurations during insertion attempts. The partitioning scheme allowed for simultaneous insertion attempts for large systems, significantly improving efficiency. The algorithm was shown to be useful in the application of the site-identification by ligand competitive saturation (SILCS) co-solvent sampling approach for the protein CDK2.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Asuka A. Orr, Aoxiang Tao, Olgun Guvench, Alexander D. MacKerell
Summary: Protein-based therapeutics often face challenges of protein aggregation and high solution viscosity due to high concentrations of active protein. The charge of a protein, affected by its environment, plays a significant role in these solution behaviors. This study presents a structure-based approach called SILCS-Biologics, which predicts the effective charge of proteins by considering the competition between ions and the presence of buffers.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Mert Y. Sengul, Alexander D. MacKerell
Summary: Metal ions, particularly Mg2+, play a role in stabilizing RNA's tertiary structures. However, the atomic-level mechanisms underlying this process are not fully understood. In this study, computational techniques were combined to investigate the specific interactions between Mg2+ ions and RNA, particularly in the pseudoknot structure of the Twister ribozyme.
Article
Chemistry, Multidisciplinary
Himanshu Goel, Wenbo Yu, Alexander D. MacKerell
Summary: This article presents the application of structure- and ligand-based approaches in simulating and predicting hERG drug liability. By combining the SILCS method with physicochemical properties, predictive models for hERG blockade were developed, resulting in improved predictability and aiding in rational drug design to minimize hERG risk.
CHEMISTRY-SWITZERLAND
(2022)
Article
Chemistry, Multidisciplinary
Mert Y. Sengul, Alexander D. MacKerell
Summary: The presence of polarizability in the force field improves the stability of RNA hairpin structures and leads to variations in dipole moments and ion distribution. Molecular dynamics simulations play a crucial role in modeling biomolecular systems, and the treatment of electrostatic interactions in the force field strongly affects simulation accuracy. In this study, the impact of polarization on structural properties, dipole moment distributions, and cation interactions in RNA hairpin systems is investigated using polarizable and non-polarizable nucleic acid force fields.
JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY
(2022)