Search results for " Dynamics"
showing 10 items of 4108 documents
A possible desensitized state conformation of the human α7 nicotinic receptor: A molecular dynamics study
2017
International audience; The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing. The characterization of the desensitized conformation(s) is even more complex, and only few specific characteristics have been identified. Furthermore, exp…
Revealing the Origin of the Efficiency of the De Novo Designed Kemp Eliminase HG-3.17 by Comparison with the Former Developed HG-3
2017
The design of new biocatalysts is a goal in biotechnology to improve the rate, selectivity and environmental impact of industrial chemical processes. In this regard, the use of computational techniques has provided valuable assistance in the design of new enzymes with remarkable catalytic activity. In this paper, hybrid QM/MM molecular dynamics simulations have allowed insights to be gained on the origin of the limited efficiency of a computationally designed enzyme for the Kemp elimination; the HG-3. Comparison of results derived from this enzyme with those of a more evolved protein containing additional point mutations, HG-3.17, rendered important information that should be taken into acc…
Mechanistic study of the biosynthesis of R-phenylcarbinol by acetohydroxyacid synthase enzyme using hybrid quantum mechanics/molecular mechanics simu…
2021
Abstract The biosynthesis of R-phenylacetylcarbinol (R-PAC) by the acetohydroxy acid synthase, (AHAS) is addressed by molecular dynamics simulations (MD), hybrid quantum mechanics/molecular mechanics (QM/MM), and QM/MM free energy calculations. The results show the reaction starts with the nucleophilic attack of the C2α atom of the HEThDP intermediate on the Cβ atom of the carbonyl group of benzaldehyde substrate via the formation of a transition state (TS1) with the HEThDP intermediate under 4′-aminopyrimidium (APH+) form. The calculated activation free energy for this step is 17.4 kcal mol−1 at 27 °C. From this point, the reaction continues with the abstraction of Hβ atom of the HEThDP in…
Photocatalytic Activity of Polymer Nanoparticles Modulates Intracellular Calcium Dynamics and Reactive Oxygen Species in HEK-293 Cells
2018
Optical modulation of living cells activity by light-absorbing exogenous materials is gaining increasing interest, due to the possibility both to achieve high spatial and temporal resolution with a minimally invasive and reversible technique and to avoid the need of viral transfection with light-sensitive proteins. In this context, conjugated polymers represent ideal candidates for photo-transduction, due to their excellent optoelectronic and biocompatibility properties. In this work, we demonstrate that organic polymer nanoparticles, based on poly(3-hexylthiophene) conjugated polymer, establish a functional interaction with an in vitro cell model (Human Embryonic Kidney cells, HEK-293). Th…
Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo-Switchable Fluorescent Protein
2015
Reversibly switchable fluorescent proteins (RSFPs) are essential for high-resolution microscopy of biological samples, but the reason why these proteins are photochromic is still poorly understood. To address this problem, we performed molecular dynamics simulations of the fast switching Met159Thr mutant of the RSFP Dronpa. Our simulations revealed a ground state structural heterogeneity in the chromophore pocket that consists of three populations with one, two, or three hydrogen bonds to the phenolate moiety of the chromophore. By means of non-adiabatic quantum mechanics/molecular dynamics simulations, we demonstrated that the subpopulation with a single hydrogen bond is responsible for of…
The biology of color
2017
In living color Animals live in a colorful world, but we rarely stop to think about how this color is produced and perceived, or how it evolved. Cuthill et al. review how color is used for social signals between individual animals and how it affects interactions with parasites, predators, and the physical environment. New approaches are elucidating aspects of animal coloration, from the requirements for complex cognition and perception mechanisms to the evolutionary dynamics surrounding its development and diversification. Science , this issue p. eaan0221
Sustainability of Fishing Is about Abundance: A Response to Bernatchez et al.
2018
Overfishing together with uncertainty or lack of recovery are characteristic challenges to fisheries management [1]. To realistically account for the multiple drivers of fish population abundances, ecosystem-based fisheries management has been accepted as the future avenue to assess and manage fisheries. However, practical implementations of ecosystem-based fisheries management remain rare, largely because of the lack of methodology and skills [2]. The discrepancy between the aims to conduct ecosystem-based and scientifically sound fisheries management and the prevailing practices becomes even wider when contrasting developed and developing countries [3].
Importance of Sequence and Timing in Parasite Coinfections
2019
Coinfections by multiple parasites predominate in the wild. Interactionsbetween parasites can be antagonistic, neutral, or facilitative, and they canhave significant implications for epidemiology, disease dynamics, and evolu-tion of virulence. Coinfections commonly result from sequential exposure ofhosts to different parasites. We argue that the sequential nature of coinfectionsis important for the consequences of infection in both natural and man-madeenvironments. Coinfections accumulate during host lifespan, determining thestructure of the parasite infracommunity. Interactions within the parasite com-munity and their joint effect on the host individual potentially shape evolution ofparasi…
Anatomical Variations in the Sinoatrial Nodal Artery: A Meta-Analysis and Clinical Considerations
2016
Background and Objective The sinoatrial nodal artery (SANa) is a highly variable vessel which supplies blood to the sinoatrial node (SAN). Due to its variability and susceptibility to iatrogenic injury, our study aimed to assess the anatomy of the SANa and determine the prevalence of its anatomical variations. Study Design An extensive search of major electronic databases was performed to identify all articles reporting anatomical data on the SANa. No lower date limit or language restrictions were applied. Anatomical data regarding the artery were extracted and pooled into a meta-analysis. Results Sixty-six studies (n = 21455 hearts) were included in the meta-analysis. The SANa usually aros…
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…