Recent progress in general force fields of small molecules

AbstractSterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate a wide variety of genes involved in cholesterol and fatty acid synthesis. After transcription, SREBPs are controlled at multiple post-transcriptional levels, including proteolytic processing and post-translational modification. Among these, proteolytic processing is a crucial regulatory step that activates SREBPs, which are synthesized as inactive endoplasmic reticulum membrane proteins. In this review, we focus on recent progress with regard to signaling pathways and small molecules that affect activation of SREBPs by proteolytic processing.

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Benchmark Assessment of Molecular Geometries and Energies from Small Molecule Force Fields

10.26434/chemrxiv.12551867 ◽

2020 ◽

Author(s):

Victoria T. Lim ◽

David F. Hahn ◽

Gary Tresadern ◽

Christopher I. Bayly ◽

David Mobley

Keyword(s):

Force Field ◽

Small Molecules ◽

Force Fields ◽

Molecular Structures ◽

Property Prediction ◽

Benchmark Assessment ◽

Heavy Atoms ◽

Comparable Level ◽

Optimized Geometries

<div>Force fields are used in a wide variety of contexts for classical molecular simulation, including studies on protein-ligand binding, membrane permeation, and thermophysical property prediction. The quality of these studies relies on the quality of the force fields used to represent the systems. </div><div>Focusing on small molecules of fewer than 50 heavy atoms, our aim in this work is to compare nine force fields: GAFF, GAFF2, MMFF94, MMFF94S, OPLS3e, SMIRNOFF99Frosst, and the Open Force Field Parsley, versions 1.0, 1.1 and 1.2. On a dataset comprising 22,675 molecular structures of 3,271 molecules, we analyzed force field-optimized geometries and conformer energies compared these to reference quantum mechanical (QM) data. We show that while OPLS3e performs best, the latest Open Force Field Parsley release is approaching a comparable level of accuracy in reproducing QM geometries and energetics for this set of molecules. Meanwhile, the performance of established force fields such as MMFF94s and GAFF2 is generally somewhat worse. We also find that the series of recent Open Force Field versions provide significant increases in accuracy. Our molecule set and results are available for other researchers to use in testing.</div>

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Benchmark assessment of molecular geometries and energies from small molecule force fields

F1000Research ◽

10.12688/f1000research.27141.1 ◽

2020 ◽

Vol 9 ◽

pp. 1390

Author(s):

Victoria T. Lim ◽

David F. Hahn ◽

Gary Tresadern ◽

Christopher I. Bayly ◽

David L. Mobley

Keyword(s):

Force Field ◽

Small Molecules ◽

Force Fields ◽

Molecular Structures ◽

Benchmark Assessment ◽

Heavy Atoms ◽

Extensive Test ◽

Better Than ◽

Optimized Geometries

Background: Force fields are used in a wide variety of contexts for classical molecular simulation, including studies on protein-ligand binding, membrane permeation, and thermophysical property prediction. The quality of these studies relies on the quality of the force fields used to represent the systems. Methods: Focusing on small molecules of fewer than 50 heavy atoms, our aim in this work is to compare nine force fields: GAFF, GAFF2, MMFF94, MMFF94S, OPLS3e, SMIRNOFF99Frosst, and the Open Force Field Parsley, versions 1.0, 1.1, and 1.2. On a dataset comprising 22,675 molecular structures of 3,271 molecules, we analyzed force field-optimized geometries and conformer energies compared to reference quantum mechanical (QM) data. Results: We show that while OPLS3e performs best, the latest Open Force Field Parsley release is approaching a comparable level of accuracy in reproducing QM geometries and energetics for this set of molecules. Meanwhile, the performance of established force fields such as MMFF94S and GAFF2 is generally somewhat worse. We also find that the series of recent Open Force Field versions provide significant increases in accuracy. Conclusions: This study provides an extensive test of the performance of different molecular mechanics force fields on a diverse molecule set, and highlights two (OPLS3e and OpenFF 1.2) that perform better than the others tested on the present comparison. Our molecule set and results are available for other researchers to use in testing.

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Improving Small Molecule Force Fields by Identifying and Characterizing Small Molecules with Inconsistent Parameters

10.26434/chemrxiv.12846602.v1 ◽

2020 ◽

Author(s):

Jordan Ehrman ◽

Victoria T. Lim ◽

Caitlin C. Bannan ◽

Nam Thi ◽

Daisy Kyu ◽

...

Keyword(s):

Force Field ◽

Small Molecules ◽

Small Molecule ◽

Force Fields ◽

Use Of Force ◽

Chemical System ◽

Simulation Methods ◽

Field Development ◽

Force Field Development ◽

Atomic Coordinates

Many molecular simulation methods use force fields to help model and simulate molecules and their behavior in various environments. Force fields are sets of functions and parameters used to calculate the potential energy of a chemical system as a function of the atomic coordinates. Despite the widespread use of force fields, their inadequacies are often thought to contribute to systematic errors in molecular simulations. Furthermore, different force fields tend to give varying results on the same systems with the same simulation settings. Here, we present a pipeline for comparing the geometries of small molecule conformers. We aimed to identify molecules or chemistries that are particularly informative for future force field development because they display inconsistencies between force fields. We applied our pipeline to a subset of the eMolecules database, and highlighted molecules that appear to be parameterized inconsistently across different force fields. We then identified over-represented functional groups in these molecule sets. The molecules and moieties identified by this pipeline may be particularly helpful for future force field parameterization.

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Recent Advance in 1-D Organic Semiconductors for Waveguide Applications

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x15666180406143727 ◽

2019 ◽

Vol 16 (3) ◽

pp. 244-252 ◽

Cited By ~ 1

Author(s):

Rong Zhang ◽

Xiaobei Jin ◽

Xuwen Wen ◽

Qi Chen

Keyword(s):

Small Molecules ◽

Organic Semiconductors ◽

Recent Progress ◽

Optoelectronic Properties ◽

Size Reduction ◽

One Dimensional ◽

Good System ◽

Ordered Nanostructures ◽

Morphology Influence

One dimensional (1-D) micro-/nanostructures provide a good system to investigate the dependence of various properties on dimensionality and size reduction, especially in optoelectronic field. Organic conjugates including small molecules and polymers exhibit good optoelectronic properties and are apt to assemble into ordered nanostructures with well-defined shapes, tunable sizes and defect-free structures. In this review, we focus on recent progress of 1-D organic semiconductors for waveguide applications. Fabrication methods and materials of 1-D organic semiconductors are introduced. The morphology influence on the properties is also summarized.

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Faculty Opinions recommendation of Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718011108.793476900 ◽

2013 ◽

Author(s):

Bradley Morgan ◽

Jeffrey Warrington

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Small Molecules ◽

Recent Progress ◽

Lateral Sclerosis

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Small Molecules Targeting Biological Clock; A Novel Prospective for Anti-Cancer Drugs

Molecules ◽

10.3390/molecules25214937 ◽

2020 ◽

Vol 25 (21) ◽

pp. 4937

Author(s):

Sadia Rahman ◽

Karlo Wittine ◽

Mirela Sedić ◽

Elitza P. Markova-Car

Keyword(s):

Circadian Rhythm ◽

Small Molecules ◽

Small Molecule ◽

Environmental Conditions ◽

Recent Progress ◽

Biological Clock ◽

New Drugs ◽

Anti Cancer ◽

Growing Body ◽

Potential Use

The circadian rhythms are an intrinsic timekeeping system that regulates numerous physiological, biochemical, and behavioral processes at intervals of approximately 24 h. By regulating such processes, the circadian rhythm allows organisms to anticipate and adapt to continuously changing environmental conditions. A growing body of evidence shows that disruptions to the circadian rhythm can lead to various disorders, including cancer. Recently, crucial knowledge has arisen regarding the essential features that underlie the overt circadian rhythm and its influence on physiological outputs. This knowledge suggests that specific small molecules can be utilized to control the circadian rhythm. It has been discovered that these small molecules can regulate circadian-clock-related disorders such as metabolic, cardiovascular, inflammatory, as well as cancer. This review examines the potential use of small molecules for developing new drugs, with emphasis placed on recent progress that has been made regarding the identification of small-molecule clock modulators and their potential use in treating cancer.

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Benchmark Assessment of Molecular Geometries and Energies from Small Molecule Force Fields

10.26434/chemrxiv.12551867.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Victoria T. Lim ◽

David Mobley

Keyword(s):

Force Field ◽

Small Molecules ◽

Gas Phase ◽

Force Fields ◽

Molecular Structures ◽

Benchmark Assessment ◽

Heavy Atoms ◽

Chemical Groups ◽

Optimized Geometries

<div>Force fields are used in a wide variety of contexts for classical molecular simulation, including studies on protein-ligand binding, membrane permeation, and thermophysical property prediction. The quality of these studies relies on the quality of the force fields used to represent the systems. </div><div>Focusing on small molecules of fewer than 50 heavy atoms, our aim in this work is to compare six force fields: GAFF, GAFF2, MMFF94, MMFF94S, SMIRNOFF99Frosst, and the Open Force Field version 1.0 (Parsley) force field. On a dataset comprising over 26,000 molecular structures, we analyzed their force field-optimized geometries and conformer energies compared to reference quantum mechanical (QM) data. We show that most of these force fields are comparable in accuracy at reproducing gas-phase QM geometries and energetics, but that GAFF/GAFF2/Parsley do slightly better in reproducing QM energies and that MMFF94/MMFF94S perform slightly better in geometries. Parsley shows considerable improvement over its predecessor SMIRNOFF99Frosst, and we identify particular outlying chemical groups for further force field improvement.</div>

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