Recent progress in general force fields of small molecules

He, Xibing; Walker, Brandon; Man, Viet Hoang; Ren, Pengyu; Wang, Junmei

doi:10.1016/j.sbi.2021.11.011

Cited by 30 publications

(20 citation statements)

References 49 publications

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“…The molecular dynamics of a complex was carried out using GROMACS version 3.3.1 using the force field CHARMM 36 m. The choice of this force field was due to the possibility of describing a wide range of chemical groups and atoms that are part of both biomacromolecules and small molecules [ 27 ]. The solvation of the system was carried out using water molecules of the TIP3 P type, which was used with CHARMM 36, thus improving the conformational space [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Piperazine Derivative Stabilizes Actin Filaments in Primary Fibroblasts and Binds G-Actin In Silico

Zernov

Ghamaryan

Makichyan

et al. 2022

CIMB

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Alzheimer’s disease (AD) is characterized by synaptic dysfunction, which is expressed through the loss of dendritic spines and changes in their morphology. Pharmacological compounds that are able to protect spines in the AD brain are suggested to be novel drugs that would be able to slow down the disease progression. We have recently shown that a positive modulator of transient receptor potential cation channel subfamily C member 6 (TRPC6), the compound N-(2-chlorophenyl)-2-(4-phenylpiperazine-1-yl) acetamide (51164), causes the upregulation of postsynaptic neuronal store-operated calcium entry, maintains mushroom spine percentage, and recovers synaptic plasticity in amyloidogenic mouse models of Alzheimer’s disease. Here, using confocal microscopy and calcium imaging methods, we present the experimental data indicating that 51164 possesses an alternative mechanism of action. We demonstrated that 51164 can increase the mushroom spine percentage in neurons with the downregulated activity of TRPC6-dependent neuronal store-operated calcium entry. Moreover, we report the binding of 51164 to G-actin in silico. We observed that 51164 interacts with Lys 336, Asp157, and Ser14 of G-actin, amino acids involved in the stabilization/polymerization of the G-actin structure. We showed that interactions of 51164 with G-actin are much stronger in comparison to the well-characterized F-actin stabilizing and polymerizing drug, jasplakinolide. The obtained results suggest an alternative protective mechanism of 51164 that is related to the preservation of actin filaments in vitro.

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Section: Methodsmentioning

confidence: 99%

Piperazine Derivative Stabilizes Actin Filaments in Primary Fibroblasts and Binds G-Actin In Silico

Zernov

Ghamaryan

Makichyan

et al. 2022

CIMB

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“…The most important recent enhancement to the standard potential is the inclusion of polarization effects explicitly. 64,65 In general, the force-field approach has proven extremely successful, however, a high accuracy in the results is closely correlated to the fact that the simulated system of interest is constructed from a set of similar previously parametrized chemical moieties. Force fields of this sort are empirically optimized to reproduce internal molecular degrees of freedom calculated through quantum mechanics (QM) and some limited experimental properties.…”

Section: Force Fieldsmentioning

confidence: 99%

Molecular modelling of the thermophysical properties of fluids: expectations, limitations, gaps and opportunities

Tillotson

Diamantonis

Buda³

et al. 2023

Phys. Chem. Chem. Phys.

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“…Two recent reviews compare FFs for small molecules. He and co-workers focus on the evaluation of free energies of solvation, 26 while Lewis-Atwell et al describe how well the conformational energy landscape of small molecules in the gas phase is described by FFs. 27 Arguably, the main aim of a general FF is to predict the properties of molecules in any environment.…”

Section: Introductionmentioning

confidence: 99%

An Imbalance in the Force: The Need for Standardized Benchmarks for Molecular Simulation

Kříž

Schmidt

Andersson

et al. 2023

J. Chem. Inf. Model.

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Force fields (FFs) for molecular simulation have been under development for more than half a century. As with any predictive model, rigorous testing and comparisons of models critically depends on the availability of standardized data sets and benchmarks. While such benchmarks are rather common in the fields of quantum chemistry, this is not the case for empirical FFs. That is, few benchmarks are reused to evaluate FFs, and development teams rather use their own training and test sets. Here we present an overview of currently available tests and benchmarks for computational chemistry, focusing on organic compounds, including halogens and common ions, as FFs for these are the most common ones. We argue that many of the benchmark data sets from quantum chemistry can in fact be reused for evaluating FFs, but new gas phase data is still needed for compounds containing phosphorus and sulfur in different valence states. In addition, more nonequilibrium interaction energies and forces, as well as molecular properties such as electrostatic potentials around compounds, would be beneficial. For the condensed phases there is a large body of experimental data available, and tools to utilize these data in an automated fashion are under development. If FF developers, as well as researchers in artificial intelligence, would adopt a number of these data sets, it would become easier to compare the relative strengths and weaknesses of different models and to, eventually, restore the balance in the force.

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Recent progress in general force fields of small molecules

Cited by 30 publications

References 49 publications

Piperazine Derivative Stabilizes Actin Filaments in Primary Fibroblasts and Binds G-Actin In Silico

Piperazine Derivative Stabilizes Actin Filaments in Primary Fibroblasts and Binds G-Actin In Silico

Molecular modelling of the thermophysical properties of fluids: expectations, limitations, gaps and opportunities

An Imbalance in the Force: The Need for Standardized Benchmarks for Molecular Simulation

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