A jumping crystal predicted with molecular dynamics and analysed with TLS refinement against powder diffraction data

Streek, Jacco van de; Alig, Edith; Parsons, Simon; Vella‐Żarb, Liana

doi:10.1107/s205225251801686x

Cited by 5 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Solving the molecular structure of such products requires, therefore, X-ray powder diffraction (XRD). Here, MD can assist by simulating the dehydration process; the XRD pattern of the dehydrated state found in the simulation can then be compared with an experimental powder pattern to solve the structure of the new phase [442,443]. Using MD-based free-energy perturbation methods, the free energy of inclusion of a solvated molecule can be calculated, which is relevant for understanding the stability of a hydrate [444].…”

Section: Studies Of Crystalline and Amorphous Solidsmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

View full text Add to dashboard Cite

Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lead optimization phases, MD facilitates the evaluation of the binding energetics and kinetics of the ligand-receptor interactions, therefore guiding the choice of the best candidate molecules for further development. The importance of considering the biological lipid bilayer environment in the MD simulations of membrane proteins is also discussed, using G-protein coupled receptors and ion channels as well as the drug-metabolizing cytochrome P450 enzymes as relevant examples. Lastly, we discuss the emerging role of MD simulations in facilitating the pharmaceutical formulation development of drugs and candidate drugs. Specifically, we look at how MD can be used in studying the crystalline and amorphous solids, the stability of amorphous drug or drug-polymer formulations, and drug solubility. Moreover, since nanoparticle drug formulations are of great interest in the field of drug delivery research, different applications of nano-particle simulations are also briefly summarized using multiple recent studies as examples. In the future, the role of MD simulations in facilitating the drug development process is likely to grow substantially with the increasing computer power and advancements in the development of force fields and enhanced MD methodologies.

show abstract

Section: Studies Of Crystalline and Amorphous Solidsmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Classical molecular dynamics (C-MD) is much more affordable and can deal with computational boxes of hundreds or thousands of molecules, and, at variance with simple minimization procedures, it can explicitly account for finite T and p effects. C-MD requires careful calibration of intermolecular potentials; besides, being an equipartition-regime technique, it suffers from the absence of quantum effects. , Its results are however quite trustworthy at or around room temperatures as demonstrated by a vast literature. ,− Its performance in high pressure or anisotropic environments need be carefully validated, and this will be one of the aims of the present paper.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulation of Molecular Crystals under Anisotropic Compression: Bulk and Directional Effects in Anthracene and Paracetamol

Rizzato

Gavezzotti

Presti

2020

Crystal Growth & Design

View full text Add to dashboard Cite

Parrinello−Rahman pressure-control algebra with an anisotropic external stress field, coupled with recently developed, accurate atom−atom potentials, has been incorporated into new modules of the Milano Chemistry Molecular Simulation (MiCMoS) computer program package for application in molecular dynamics (MD) simulations for organic crystals. Simulations were carried out for two widely different intermolecular environments, anthracene and paracetamol. The results reproduce quantitatively the anisotropic evolution obtained by pressure-dependent X-ray diffraction experiments in hydrostatic conditions. A less usual application concerns the probing of differently oriented uniaxial stresses, which for anthracene reveal a phase transition triggered by mechanical excitation along a direction parallel to the main molecular axis. For paracetamol, differences in compressibility along different crystal directions are borne out and are explained in molecular terms with reference to the hydrogen bonding scheme. Simulations of tensile stress, that is, negative pressure along different crystal directions, provide an estimate of yield points in a range of 0.2−0.5 GPa (2000−5000 atm) and indicate the weakest directions. On the basis of these results, we strongly suggest that classical MD in the atom−atom formulation, even in the absence of thorough treatment of quantum effects, but endowed with flexible algebra and coupled with carefully calibrated intermolecular potentials, can give reliable results of quantitative and semiquantitative character on the structural dynamics of organic crystals, providing an essential support to downstream studies of mechanical, optical, and electronic properties. Widespread use for further experience and validation is encouraged by the availability of the Fortran source codes.

show abstract

“…This suggests that the librations are strongly influenced by the phase transition and are not well-defined in the β-polymorph. A recently study on thermosalient crystals of perhydropyrene, which is a polycyclic hydrocarbon similarly to coronene, showed that the librations play key roles in the thermosalient phase transition 33 . Therefore, it is suggested that the librations are also critically involved in the phase transition of the coronene nanofibers.…”

Section: Resultsmentioning

confidence: 99%

Phase-transition-induced jumping, bending, and wriggling of single crystal nanofibers of coronene

Takazawa

Inoue

Mitsuishi

et al. 2021

Sci Rep

View full text Add to dashboard Cite

For decades, it has been reported that some organic crystals suddenly crack, break, or jump when they are heated from room temperature. Recently, such crystals have been intensively studied both in fundamental science and for high-speed mechanical device applications. According to these studies, the sudden crystal motions have been attributed to structural phase transitions induced by heating. Stress created by the phase transition is released through the sudden and rapid motion of the crystals. Here we report that single crystal nanofibers of coronene exhibit a new type of ultrafast motion when they are cooled from room temperature and subsequently heated to room temperature. The nanofibers make centimeter-scale jumps accompanied by surprisingly unique behaviors such as sharp bending and wriggling. We found that the motions are caused by a significantly fast structural phase transition between two polymorphs of coronene. A theoretical investigation revealed that the sudden force generated by the phase transition together with the nanoscale dimensions and elastic properties create dynamical instability in the nanofibers that results in the motions. Our finding demonstrates the novel mechanism that leads to ultrafast, large deformation of organic crystals.

show abstract

A jumping crystal predicted with molecular dynamics and analysed with TLS refinement against powder diffraction data

Abstract: A phase transition in a jumping crystal is predicted using molecular dynamics. The resulting structure and the dynamics of the transition are verfied by TLS refinement against powder diffraction data.

Cited by 5 publications

References 39 publications

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulation of Molecular Crystals under Anisotropic Compression: Bulk and Directional Effects in Anthracene and Paracetamol

Phase-transition-induced jumping, bending, and wriggling of single crystal nanofibers of coronene

Contact Info

Product

Resources

About