scholarly journals Three-dimensional structure of Megabalanus rosa Cement Protein 20 revealed by multi-dimensional NMR and molecular dynamics simulations

2019 ◽  
Vol 374 (1784) ◽  
pp. 20190198 ◽  
Author(s):  
Harini Mohanram ◽  
Akshita Kumar ◽  
Chandra S. Verma ◽  
Konstantin Pervushin ◽  
Ali Miserez
Keyword(s):  
Molecular Dynamics ◽  
Disulfide Bonds ◽  
Molecular Mechanisms ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Md Simulations ◽  
Dimensional Structure ◽  
Nmr Studies ◽  
Dynamics Simulations ◽  
Cement Protein

Barnacles employ a protein-based cement to firmly attach to immersed substrates. The cement proteins (CPs) have previously been identified and sequenced. However, the molecular mechanisms of adhesion are not well understood, in particular, because the three-dimensional molecular structure of CPs remained unknown to date. Here, we conducted multi-dimensional nuclear magnetic resonance (NMR) studies and molecular dynamics (MD) simulations of recombinant Megabalanus rosa Cement Protein 20 ( r MrCP20). Our NMR results show that r MrCP20 contains three main folded domain regions intervened by two dynamic loops, resulting in multiple protein conformations that exist in equilibrium. We found that 12 out of 32 Cys in the sequence engage in disulfide bonds that stabilize the β -sheet domains owing to their placement at the extremities of β -strands. Another feature unveiled by NMR is the location of basic residues in turn regions that are exposed to the solvent, playing an important role for intermolecular contact with negatively charged surfaces. MD simulations highlight a highly stable and conserved β -motif ( β 7- β 8), which may function as nuclei for amyloid-like nanofibrils previously observed in the cured adhesive cement. To the best of our knowledge, this is the first report describing the tertiary structure of an extracellular biological adhesive protein at the molecular level. This article is part of the theme issue ‘Transdisciplinary approaches to the study of adhesion and adhesives in biological systems’.

scholarly journals MDGRAPE-4: a special-purpose computer system for molecular dynamics simulations

2014 ◽  
Vol 372 (2021) ◽  
pp. 20130387 ◽  
Author(s):  
Itta Ohmura ◽  
Gentaro Morimoto ◽  
Yousuke Ohno ◽  
Aki Hasegawa ◽  
Makoto Taiji
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Computer System ◽  
Three Dimensional ◽  
Md Simulations ◽  
Particle Simulation ◽  
Peak Performance ◽  
Dynamics Simulations ◽  
Purpose Computer ◽  
Special Purpose Computer

We are developing the MDGRAPE-4, a special-purpose computer system for molecular dynamics (MD) simulations. MDGRAPE-4 is designed to achieve strong scalability for protein MD simulations through the integration of general-purpose cores, dedicated pipelines, memory banks and network interfaces (NIFs) to create a system on chip (SoC). Each SoC has 64 dedicated pipelines that are used for non-bonded force calculations and run at 0.8 GHz. Additionally, it has 65 Tensilica Xtensa LX cores with single-precision floating-point units that are used for other calculations and run at 0.6 GHz. At peak performance levels, each SoC can evaluate 51.2 G interactions per second. It also has 1.8 MB of embedded shared memory banks and six network units with a peak bandwidth of 7.2 GB s −1 for the three-dimensional torus network. The system consists of 512 (8×8×8) SoCs in total, which are mounted on 64 node modules with eight SoCs. The optical transmitters/receivers are used for internode communication. The expected maximum power consumption is 50 kW. While MDGRAPE-4 software has still been improved, we plan to run MD simulations on MDGRAPE-4 in 2014. The MDGRAPE-4 system will enable long-time molecular dynamics simulations of small systems. It is also useful for multiscale molecular simulations where the particle simulation parts often become bottlenecks.

scholarly journals Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

2020 ◽  
Author(s):  
Sandro Bottaro ◽  
Giovanni Bussi ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Genomic Region ◽  
Dimensional Structure ◽  
Structure Based Drug Design ◽  
Stem Loop ◽  
Rna Molecules ◽  
Conformational Ensembles ◽  
Dynamics Simulations

The 5' untranslated region (UTR) of SARS-CoV-2 genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structure is not known yet. Here, we predict structure and dynamics of five RNA stem-loops in the 5'-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrengements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterisation of these systems, and provide putative three-dimensional models for structure-based drug design studies.

scholarly journals Molecular dynamics simulations of potassium channels

2007 ◽  
Vol 5 (3) ◽  
pp. 635-671 ◽  
Author(s):  
Carmen Domene
Keyword(s):  
Molecular Dynamics ◽  
Potassium Channels ◽  
Molecular Dynamics Simulations ◽  
Experimental Work ◽  
Three Dimensional ◽  
Md Simulations ◽  
Structure And Dynamics ◽  
Dynamics Simulations ◽  
New Algorithms

AbstractDespite the complexity of ion-channels, MD simulations based on realistic all-atom models have become a powerful technique for providing accurate descriptions of the structure and dynamics of these systems, complementing and reinforcing experimental work. Successful multidisciplinary collaborations, progress in the experimental determination of three-dimensional structures of membrane proteins together with new algorithms for molecular simulations and the increasing speed and availability of supercomputers, have made possible a considerable progress in this area of biophysics. This review aims at highlighting some of the work in the area of potassium channels and molecular dynamics simulations where numerous fundamental questions about the structure, function, folding and dynamics of these systems remain as yet unresolved challenges.

Molecular modelling studies of sirtuin 2 inhibitors using three-dimensional structure–activity relationship analysis and molecular dynamics simulations

2015 ◽  
Vol 11 (3) ◽  
pp. 723-733 ◽  
Author(s):  
Yu-Chung Chuang ◽  
Ching-Hsun Chang ◽  
Jen-Tai Lin ◽  
Chia-Ning Yang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Comfa Model ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Dynamics Simulations

In this work, a CoMFA model and molecular dynamics simulations provide guidelines for drug development of SIRT2 inhibitors.

scholarly journals On the Use of Molecular Dynamics Simulations for Elucidating Fine Structural, Physico-Chemical and Thermomechanical Properties of Lignocellulosic Systems: Historical and Future Perspectives

2021 ◽  
Vol 5 (2) ◽  
pp. 55
Author(s):  
Krishnamurthy Prasad ◽  
Mostafa Nikzad ◽  
Shammi Sultana Nisha ◽  
Igor Sbarski
Keyword(s):  
Molecular Dynamics ◽  
High Performance ◽  
Molecular Mechanisms ◽  
Md Simulations ◽  
Thermomechanical Properties ◽  
Current State ◽  
Physico Chemical ◽  
Carbohydrate Complex ◽  
Dynamics Simulations

The use of Molecular Dynamics (MD) simulations for predicting subtle structural, thermomechanical and related characteristics of lignocellulosic systems is studied. A historical perspective and the current state of the art are discussed. The use of parameterised MD force fields, scaling up simulations via high performance computing and intrinsic molecular mechanisms influencing the mechanical, thermal and chemical characteristics of lignocellulosic systems and how these can be predicted and modelled using MD is shown. Individual discussions on the MD simulations of the lignin, cellulose, lignin-carbohydrate complex (LCC) and how MD can elucidate the role of water on the surface and microstructural characteristics of these lignocellulosic systems is shown. In addition, the use of MD for unearthing molecular mechanisms behind lignin-enzyme interactions during precipitation processes and the deforming/structure weakening brought about by cellulosic interactions in some lignocellulosic systems is both predicted and quantified. MD results from relatively smaller systems comprised of several hundred to a few thousand atoms and massive multi-million atom systems are both discussed. The versatility and effectiveness of MD based on its ability to provide viable predictions from both smaller and massive starting systems is presented in detail.

scholarly journals Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 301 ◽  
Author(s):  
Jian Wang ◽  
Cun-Di Li ◽  
Lin Sun
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nk Cells ◽  
Disulfide Bonds ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Three Dimensional ◽  
Adaptor Protein ◽  
Protein Molecule ◽  
Hepatoma Cells ◽  
Dimensional Structure

Hepatocellular carcinoma is a common malignant tumor with high mortality. Its malignant proliferation, invasion, and metastasis are closely related to the cellular immune function of the patients. NKG2D is a key activated and type II membrane protein molecule expressed on the surface of almost all NK cells. The human NKG2D gene is 270 kb long, located at 12p12.3–p13.1, and contains 10 exons and 9 introns. The three-dimensional structure of the NKG2D monomeric protein contains two alpha-helices, two beta-lamellae, and four disulfide bonds, and its’ signal of activation is transmitted mainly by the adaptor protein (DAP). NKG2D ligands, including MICA, MICB, and ULBPs, can be widely expressed in hepatoma cells. After a combination of NKG2D and DAP10 in the form of homologous two polymers, the YxxM motif in the cytoplasm is phosphorylated and then signaling pathways are also gradually activated, such as PI3K, PLCγ2, JNK-cJunN, and others. Activated NK cells can enhance the sensitivity to hepatoma cells and specifically dissolve by releasing a variety of cytokines (TNF-α and IFN-γ), perforin, and high expression of FasL, CD16, and TRAIL. NK cells may specifically bind to the over-expressed MICA, MICB, and ULBPs of hepatocellular carcinoma cells through the surface activating receptor NKG2D, which can help to accurately identify hepatoma, play a critical role in anti-hepatoma via the pathway of cytotoxic effects, and obviously delay the poor progress of hepatocellular carcinoma.

Effect of Length and Cross-Sectional Area on Ni3Fe Alloy Plasticity

2014 ◽  
Vol 1013 ◽  
pp. 242-248 ◽  
Author(s):  
Mikhail D. Starostenkov ◽  
Mohamed Mahmud Aish
Keyword(s):  
Molecular Dynamics ◽  
Three Dimensional ◽  
Computer Experiment ◽  
Md Simulations ◽  
Deformation Energy ◽  
Cross Sectional Area ◽  
Face Centered Cubic ◽  
Sectional Area ◽  
Cross Sectional ◽  
Dynamics Simulations

Molecular Dynamics (MD) simulations have been carried out on ultrathin Ni3Fe alloy with face-centered cubic (FCC) lattice upon application of uniaxial tension at nanolevel with a speed of 20 m/s. the deformation corresponds to the direction <001>. To the calculated block of crystal - free boundary conditions are applied in the directions <100>, <010>. Morse potential was employed to carry out three dimensional molecular dynamics simulations. A computer experiment is performed at a temperature corresponding to 300 K. MD simulation used to investigate the effect of long of ultrathin Ni3Fe alloy on the nature of deformation and fracture. The engineering stress–time diagrams obtained by the MD simulations of the tensile specimens of these ultrathin Ni3Fe alloy show a rapid increase in stress up to a maximum followed by a gradual drop to zero when the specimen fails by ductile fracture. The feature of deformation energy can be divided into four regions: quasi-elastic, plastic, flow and failure. The yield strength decreased with increasing long of alloy, but increases with increasing the cross sectional area. Plasticity disappear when the length of the allays is too large. The results showed that breaking position depended on the alloy length.

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