Molecular modeling of neurological membrane proteins − from binding sites to synapses. (1st May 2019)

• Record Type: Journal Article
• Authors: Ladefoged, Lucy Kate; Zeppelin, Talia; Schiøtt, Birgit
• Is Part Of: Neuroscience letters. Volume 700(2019)
• Page Start: 38
• Page End: 49
• Publication Date: 2019-05-01
• Subjects: TFLOPS tera floating point operations per second -- CG coarse-grained -- AA all-atom -- QM quantum mechanics -- MD molecular dynamics -- MAT monoamine transporter -- GPCR G-protein coupled receptor -- IFD induced fit docking -- SERT serotonin transporter -- DA dopamine -- DAT dopamine transporter -- PaMLAC paired mutant-ligand analogue complementation -- QPLD quantum polarized ligand docking -- LeuT leucine transporter -- MSM Markov state model -- NMDA N-methyl-d-aspartate -- DAFT docking assay for transmembrane components -- PMF potential of mean force -- PIP2 phosphatidylinositol 4, 5-bisphosphate -- PC phosphatidylcholine -- PE phosphatidylethanolamine -- PS phosphatidylserine -- LPC lysophosphatidylcholine -- LPE lysophosphatidylethanolamine -- aMD accelerated molecular dynamics -- RAMD random accelerated molecular dynamics -- TI thermodynamic integration -- MM-PBSA molecular mechanics − Poisson Boltzmann, surface area -- ABF adaptive biasing force; Molecular docking -- Molecular dynamics -- Enhanced sampling -- Free energy calculations -- Monoamine transporters -- Membrane proteins; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.05.034
• Languages: English
• ISSNs: 0304-3940

Abstract

Graphical abstract: Highlights: Comprehensive review of modelling studies of monoamine transporters. Covers methods from molecular docking to advanced MD simulations. Presenting future directions with complex lipids mixtures. Simple explanations of advanced methods for protein modelling. Abstract: The field of molecular mechanics studies of proteins has developed enormously since its origin in the 1970's, and many applications and methodologies have branched from the original idea of the force field. The applications of such methodologies are far spread and commonplace in neuroscience research today. In this mini-review, we outline the main methodologies applied when studying events ranging from ligands binding within small binding sites, through overall large-scale conformational changes, to the even larger-scale oligomerization events of neurological membrane proteins. The limitations and caveats of the methods are discussed, while examples of recent applications are described and their implications discussed. We have chosen to focus on the monoamine transporters throughout, with a few examples from neurological membrane proteins such as ionotropic and metabotropic neurotransmitter receptors.