Computer-Aided Drug Design in Research on Chinese Materia Medica: Methods, Applications, Advantages, and Challenges

Pharmaceutics, Год журнала: 2025, Номер 17(3), С. 315 - 315

Опубликована: Март 1, 2025

Chinese materia medica (CMM) refers to the medicinal substances used in traditional medicine. In recent years, CMM has become globally prevalent, and scientific research on increasingly garnered attention. Computer-aided drug design (CADD) been employed Western medicine for many contributing significantly its progress. However, role of CADD not systematically reviewed. This review briefly introduces methods from perspectives computational chemistry (including quantum chemistry, molecular mechanics, mechanics/molecular mechanics) informatics cheminformatics, bioinformatics, data mining). Then, it provides an exhaustive discussion applications these through rich cases. Finally, outlines advantages challenges research. conclusion, despite current challenges, still offers unique over experiments. With development industry computer science, especially driven by artificial intelligence, is poised play pivotal advancing

Язык: Английский

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Learning Multiple Potential Energy Surfaces by Automated Discovery of a Compatible Representation

Journal of Chemical Theory and Computation, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Creating analytic representations of multiple potential energy surfaces for modeling electronically nonadiabatic processes is a major challenge being addressed in various ways by the chemical dynamics community. In this work, we introduce new method that can achieve convenient learning (PESs) and their gradients (negatives forces) polyatomic system. This method, called compatibilization deep neural network (CDNN), demonstrated to be accurate and, even more importantly, automatic. The only required input database with geometries energies. produces matrix, compatible matrix (CPEM), may interpreted as electronic Hamiltonian an implicit basis, adiabatic are obtained diagonalization automatic differentiation. We show CPEM, which neither nor necessarily diabatic, discovered automatically during procedure special design CDNN architecture. believe will very useful practice coupled PESs systems because it fully

Язык: Английский

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PyDFT-QMMM: A modular, extensible software framework for DFT-based QM/MM molecular dynamics

The Journal of Chemical Physics, Год журнала: 2024, Номер 161(3)

Опубликована: Июль 15, 2024

PyDFT-QMMM is a Python-based package for performing hybrid quantum mechanics/molecular mechanics (QM/MM) simulations at the density functional level of theory. The program designed to treat short-range and long-range interactions through user-specified combinations electrostatic mechanical embedding procedures within periodic simulation domains, providing necessary interfaces external chemistry molecular dynamics software. To enable direct electrostatics in systems, we have derived implemented force terms our previously described QM/MM/PME approach [Pederson McDaniel, J. Chem. Phys. 156, 174105 (2022)]. Communication with software packages Psi4 OpenMM facilitated Python application programming (APIs). core library contains basic utilities running QM/MM simulations, plug-in entry-points are provided users implement custom energy/force calculation integration routines, an extensible architecture. user interacts primarily its API, allowing complex workflow development scripting, example, interfacing PLUMED free energy simulations. We provide benchmarks forces conservation alternative approaches. further demonstrate simple example use case water solute solvent system, which radial distribution functions computed from 100 ps simulations; this highlight how solvation structure sensitive different basis-set choices due under- or over-polarization QM molecule’s electron density.

Язык: Английский

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How Accurate Are QM/MM Models?

The Journal of Physical Chemistry A, Год журнала: 2024, Номер unknown

Опубликована: Дек. 4, 2024

Despite the success and widespread use of QM/MM methods in modeling (bio)chemically important processes, their accuracy is still not well understood. A key reason because these are ultimately approximations to direct QM calculations very large systems, which impractical perform most cases. We highlight recent progress toward development realistic model systems where it possible obtain full reference data directly systematically evaluate effectiveness different generation schemes. These highly flexible can be tailored probe sensitivity a reaction types simulation parameters such as pairing MM potentials, region size, composition. It envisaged that this strategy could used validate schemes spur more robust models future.

Язык: Английский

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The development of the QM/MM interface and its application for the on-the-fly QM/MM nonadiabatic dynamics in JADE package: Theory, implementation, and applications

The Journal of Chemical Physics, Год журнала: 2024, Номер 160(23)

Опубликована: Июнь 17, 2024

Understanding the nonadiabatic dynamics of complex systems is a challenging task in computational photochemistry. Herein, we present an efficient and user-friendly quantum mechanics/molecular mechanics (QM/MM) interface to run on-the-fly dynamics. Currently, this consists independent set codes designed for general-purpose use. demonstrate ability feasibility QM/MM by integrating it with our long-term developed JADE package. Tailored handle processes various systems, especially condensed phases protein environments, delve into theories, implementations, applications The approach established within framework additive scheme, employing electrostatic embedding, link-atom inclusion, charge-redistribution schemes treat boundary. Trajectory surface-hopping are facilitated using fewest switches algorithm, encompassing classical treatments nuclear electronic motions, respectively. Finally, report simulations two typical systems: azomethane water retinal chromophore PSB3 environment. Our results not only illustrate power program but also reveal important roles environmental factors processes.

Язык: Английский

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Fluoride Ion Binding and Translocation in the CLC^F Fluoride/Proton Antiporter: Molecular Insights from Combined Quantum-Mechanical/Molecular-Mechanical Modeling

The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(11), С. 2697 - 2706

Опубликована: Март 6, 2024

CLC

Язык: Английский

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Multiscale biomolecular simulations in the exascale era

Current Opinion in Structural Biology, Год журнала: 2024, Номер 86, С. 102821 - 102821

Опубликована: Апрель 29, 2024

The complexity of biological systems and processes, spanning molecular to macroscopic scales, necessitates the use multiscale simulations get a comprehensive understanding. Quantum mechanics/molecular mechanics (QM/MM) dynamics (MD) are crucial for capturing processes beyond reach classical MD simulations. advent exascale computing offers unprecedented opportunities scientific exploration, not least within life sciences, where essential unravel intricate mechanisms underlying processes. However, leveraging immense computational power requires innovative algorithms software designs. In this context, we discuss current status future prospects biomolecular on supercomputers with focus QM/MM MD. We highlight our own efforts in developing versatile high-performance simulation framework aim efficient utilization state-of-the-art supercomputers. showcase its application uncovering complex potential computing.

Язык: Английский

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Plugin-based interoperability and ecosystem management for the MolSSI Driver Interface Project

The Journal of Chemical Physics, Год журнала: 2024, Номер 160(21)

Опубликована: Июнь 4, 2024

The MolSSI Driver Interface (MDI) Project is an effort to simplify and standardize the process of enabling tight interoperability between independently developed code bases supported by numerous software packages across domain chemical physics. It enables a wide variety use cases, including quantum mechanics/molecular mechanics, advanced sampling, path integral molecular dynamics, machine learning, ab initio etc. We describe two major developments within MDI that provide novel solutions key challenges. first these development Plugin System, which allows MDI-supporting libraries be used as highly modular plugins, with enforcing standardized application programming interface plugins. Codes can plugins without linking against them during their build process, end-users select plugin(s) they wish at runtime. System features sophisticated callback system codes interact on granular level represents significant advancement toward increased modularity among scientific codes. second Mechanic, ecosystem management tool utilizes Docker containerization developing, validating, maintaining, deploying Additionally, Mechanic provides framework for launching simulations in each interoperating executed separate computational environment. This eliminates need compile multiple production single environment, reducing opportunities dependency conflicts lowering barrier entry users MDI-enabled

Язык: Английский

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MiMiC: A high-performance framework for multiscale molecular dynamics simulations

The Journal of Chemical Physics, Год журнала: 2024, Номер 161(2)

Опубликована: Июль 11, 2024

MiMiC is a framework for performing multiscale simulations in which loosely coupled external programs describe individual subsystems at different resolutions and levels of theory. To make it highly efficient flexible, we adopt an interoperable approach based on multiple-program multiple-data (MPMD) paradigm, serving as intermediary responsible fast data exchange interactions between the subsystems. The main goal to avoid interfering with underlying parallelization programs, including operability hybrid architectures (e.g., CPU/GPU), keep their setup execution close possible original. At moment, offers implementation electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) that has demonstrated unprecedented parallel scaling large biomolecules using CPMD GROMACS QM MM engines, respectively. However, designed high flexibility general models mind, can be straightforwardly extended beyond QM/MM. In this article, illustrate software design features framework, compelling choice upcoming era exascale high-performance computing.

Язык: Английский

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Reshaping the QM Region On-the-Fly: Adaptive-Shape QM/MM Dynamic Simulations of a Hydrated Proton in Bulk Water

Journal of Chemical Theory and Computation, Год журнала: 2024, Номер 20(9), С. 3462 - 3472

Опубликована: Апрель 26, 2024

Adaptive quantum mechanics/molecular mechanics (QM/MM) reclassifies on-the-fly a molecule or molecular fragment as QM MM during dynamics simulations without abrupt changes in the energy forces. Notably, permuted adaptive-partitioning (PAP) algorithms have been applied to simulate hydrated proton, with mobile zone anchored at pseudoatom called proton indicator. The position of indicator approximates location delocalized excess yielding smooth trajectory diffusing via Grotthuss mechanism aqueous solutions. zone, which has taken be sphere preset radius, follows wherever it goes. Although are successful, use spherical one disadvantage: A large radius must utilized minimize chance missing water molecules that important translocation. leads is computationally expensive. In this work, we report new way set up where includes only transfer. importance given quantified by its "weight" depends on relation reaction path weight varies smoothly, ensuring gradually appears disappears from changes, required PAP method. Consequently, shape evolves on-the-fly, keeping small possible and necessary. Test demonstrate algorithm significantly improves computation efficiency while maintaining proper descriptions transfer bulk water.

Язык: Английский

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