Perspective: Computational modeling of accurate cellular membranes with molecular resolution

Klauda, Jeffery B.

doi:10.1063/1.5055007

Cited by 23 publications

(26 citation statements)

References 142 publications

(161 reference statements)

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“…Early simulations of membrane proteins were performed without membrane embedding, but today accurate membrane modeling has allowed for the simulation of realistic cellular membrane environments [357,358]. In vitro data on membrane thickness, curvature, fluidity [359], and surface tension [360] has enabled accurate modeling of ligand binding and the corresponding downstream activation of the signaling proteins [361,362].…”

Section: Molecular Dynamics Simulations Of Gpcrs and Ion Channelsmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

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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.

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Section: Molecular Dynamics Simulations Of Gpcrs and Ion Channelsmentioning

confidence: 99%

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

et al. 2020

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“…Other FF parameters such as the ones for bonds, missing values for dihedrals, and Urey-Bradley and angular parameters were inherited from ''old'' atom types (CTL5, NH3L, and CTL2) of the SLipids FF [34][35][36] and the CHARMM36 FF. [51][52][53] MD simulation set-ups…”

Section: Models and Simulation Setupmentioning

confidence: 99%

DOPC versus DOPE as a helper lipid for gene-therapies: molecular dynamics simulations with DLin-MC3-DMA

Ermilova

Swenson

2020

Phys. Chem. Chem. Phys.

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“…Molecular dynamic (MD) simulations have predicted that water operates cooperatively with structural changes for the phospholipid membrane 9 . Lamellar structures have also been investigated in aqueous solutions by MD, in which detailed features were captured in membranes with molecular resolutions 10,11 . Dissipative particle dynamic (DPD) simulation suggests that vesicle structures can be observed in the simple model of phospholipid–water mixtures when chain lengths and amphiphilicity are suitable 12 .…”

Section: Introductionmentioning

confidence: 99%

Shear-induced microstructures and dynamics processes of phospholipid cylinders in solutions

Shan

Qiang

et al. 2019

Sci Rep

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Shear-induced microstructures and their corresponding dynamic processes are investigated for phospholipid cylinders in aqueous solution by dissipative particle dynamic simulation. Various phospholipid cylinders with cross-sections, which are formed under shear-free flow, are selected to examine the effects of shear flow on their structures and dynamic processes. Shear flow induces the transition from cylinders into vesicles at weak rate and the transition into vesicle–lamella mixtures with increased shear rate and lamella structures at the strong shear rate. Then, the average radius of gyration and shape factors of the polymer chains in the dynamic processes are discussed in detail. Results show that shear flow causes the structure of the polymer chains to be elongated along the shear direction, and the configuration of the polymer chain can be rapidly transformed into an ellipsoid structure under strong shear.

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Perspective: Computational modeling of accurate cellular membranes with molecular resolution

Cited by 23 publications

References 142 publications

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development

DOPC versus DOPE as a helper lipid for gene-therapies: molecular dynamics simulations with DLin-MC3-DMA

Shear-induced microstructures and dynamics processes of phospholipid cylinders in solutions

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