Search results for "molekyylidynamiikka"
showing 10 items of 40 documents
Negatively Charged Gangliosides Promote Membrane Association of Amphipathic Neurotransmitters
2018
Lipophilic neurotransmitters (NTs) such as dopamine are chemical messengers enabling neurotransmission by adhering onto the extracellular surface of the post-synaptic membrane in a synapse, followed by binding to their receptors. Previous studies have shown that the strength of the NT-membrane association is dependent on the lipid composition of the membrane. Negatively charged lipids such as phosphatidylserine, phosphatidylglycerol, and phosphatidic acid have been indicated to promote NT-membrane binding, however these anionic lipids reside almost exclusively in the intracellular leaflet of the post-synaptic membrane instead of the extracellular leaflet facing the synaptic cleft. Meanwhile…
Structural and functional insights into lysostaphin–substrate interaction
2018
Lysostaphin from Staphylococcus simulans and its family enzymes rapidly acquire prominence as the next generation agents in treatment of S. aureus infections. The specificity of lysostaphin is promoted by its C-terminal cell wall targeting domain selectivity towards pentaglycine bridges in S. aureus cell wall. Scission of these cross-links is carried out by its N-terminal catalytic domain, a zinc-dependent endopeptidase. Understanding the determinants affecting the efficiency of catalysis and strength and specificity of interactions lies at the heart of all lysostaphin family enzyme applications. To this end, we have used NMR, SAXS and molecular dynamics simulations to characterize lysostap…
A Perspective : Active Role of Lipids in Neurotransmitter Dynamics
2019
AbstractSynaptic neurotransmission is generally considered as a function of membrane-embedded receptors and ion channels in response to the neurotransmitter (NT) release and binding. This perspective aims to widen the protein-centric view by including another vital component—the synaptic membrane—in the discussion. A vast set of atomistic molecular dynamics simulations and biophysical experiments indicate that NTs are divided into membrane-binding and membrane-nonbinding categories. The binary choice takes place at the water-membrane interface and follows closely the positioning of the receptors’ binding sites in relation to the membrane. Accordingly, when a lipophilic NT is on route to a m…
Kultapinnan S(CH2)xN3-adsorbaattien laskennallinen värähdysdynamiikka ja 2DIR-spektroskopia molekyylidynamiikkamenetelmin
2018
Tehtiin MD-simulaatiot kultapinnan siltapaikkoihin kahdella eri peitolla (1/3 ja 1/4) yksikerrokseksi asetetuille pitkä- ja lyhytketjuisille S(CH2)xN3-adsorbaateille (x = 2, 11). Kukin systeemi simuloitiin sekä tyhjiössä että vesiympäristössä. Simulaatioista määritettiin atsidiryhmien FFCF:t ja CLS:t odotusaikavälille t2 ∈ [0, 200] ps. Näihin sovitettiin multieksponentiaaliset funktiot ja havaittiin FFCF:n hitaiden komponenttien vastaavan CLS-komponentteja. Lisäksi tarkasteltiin mallia, joka esittää CLS:n ja FFCF:n välille suoraviivaisen yhteyden ja mahdollistaa Lorentzin ja Gaussin leveyksien määrittämisen. Malli todettiin hyvin toimivaksi simulaatioista saatujen tulosten tapauksessa. MD s…
Protonation of the Biliverdin IXα Chromophore in the Red and Far-Red Photoactive States of a Bacteriophytochrome
2019
The tetrapyrrole chromophore biliverdin IXα (BV) in the bacteriophytochrome from Deinococcus radiodurans (DrBphP) is usually assumed to be fully protonated, but this assumption has not been systematically validated by experiments or extensive computations. Here, we use force field molecular dynamics simulations and quantum mechanics/molecular mechanics calculations with density functional theory and XMCQDPT2 methods to investigate the effect of the five most probable protonation forms of BV on structural stability, binding pocket interactions, and absorption spectra in the two photochromic states of DrBphP. While agreement with X-ray structural data and measured UV/vis spectra suggest that …
Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2
2021
The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied. Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, th…
Controlling Exciton Propagation in Organic Crystals through Strong Coupling to Plasmonic Nanoparticle Arrays.
2022
Exciton transport in most organic materials is based on an incoherent hopping process between neighboring molecules. This process is very slow, setting a limit to the performance of organic optoelectronic devices. In this Article, we overcome the incoherent exciton transport by strongly coupling localized singlet excitations in a tetracene crystal to confined light modes in an array of plasmonic nanoparticles. We image the transport of the resulting exciton–polaritons in Fourier space at various distances from the excitation to directly probe their propagation length as a function of the exciton to photon fraction. Exciton–polaritons with an exciton fraction of 50% show a propagation length…
Non-syndromic Mitral Valve Dysplasia Mutation Changes the Force Resilience and Interaction of Human Filamin A
2018
International audience; Filamin A (FLNa), expressed in endocardial endothelia during fetal valve morphogenesis, is key in cardiac development. Missense mutations in FLNa cause non-syndromic mitral valve dysplasia (FLNA-MVD). Here, we aimed to reveal the currently unknown underlying molecular mechanism behind FLNA-MVD caused by the FLNa P637Q mutation. The solved crystal structure of the FLNa3-5 P637Q revealed that this mutation causes only minor structural changes close to mutation site. These changes were observed to significantly affect FLNa's ability to transmit cellular force and to interact with its binding partner. The performed steered molecular dynamics simulations showed that signi…
Encapsulation of xenon by bridged resorcinarene cages with high 129Xe NMR chemical shift and efficient exchange dynamics
2023
Functionalized cages encapsulating xenon atoms enable highly sensitive, background-free molecular imaging through a technique known as HyperCEST 129Xe MRI. Here, we introduce a class of potential biosensor cage structures based on two resorcinarene macrocycles bridged either by aliphatic carbon chains or piperazines. First-principles-based modeling predicts a high chemical shift (about 345 ppm) outside the typical experimental observation window for 129Xe encapsulated by the aliphatically bridged cage and two 129Xe resonances for the piperazine-bridged cages corresponding to single and double loading. Based on the computational predictions as well as 129Xe chemical exchange saturation trans…
Ab initio molecular dynamics study of overtone excitations in formic acid and its water complex
2018
In this article, we present results from ab initio molecular dynamics simulation of overtone excitation in formic acid monomer and its water complex in the gas phase. For the monomer, a conformation change is observed employing both OH and CH vibrational excitations, which supports experimental findings. In the formic acid–water complex, interconversion also takes place, but it proceeds via hydrogen exchange rather than via intramolecular reaction. Simulations raise a question on effect of quantum and matrix effects to the results. Also, a brief test of different computation methods was done on the system. peerReviewed