scholarly journals Native-state dynamics of the ubiquitin family: implications for function and evolution

2005 ◽  
Vol 2 (2) ◽  
pp. 47-54 ◽  
Author(s):  
Neelan J Marianayagam ◽  
Sophie E Jackson
Keyword(s):  
Protein Function ◽  
Global Dynamics ◽  
Essential Dynamics ◽  
Native State ◽  
Dynamic Simulations ◽  
Protein Motions ◽  
Local Fluctuations ◽  
Backbone Atoms ◽  
Global And Local ◽  
Dynamics Method

Protein dynamics are integral to protein function. In recent years, the use of computer simulation to understand the molecular motions of proteins has become widespread. However, there are few such studies which compare the dynamics of proteins that are structurally and functionally related. In this study, we present native-state molecular dynamic simulations of four proteins which possess a ubiquitin-like fold. Three of these proteins are thought to have evolved from a common ancestral ubiquitin-like protein and have similarities in their function. A fourth protein, which is structurally homologous but which appears to have a different function, is also studied. Local fluctuations in the native state simulations are analysed, and conserved motions of the C-α backbone atoms are identified in residues which are important for function. In addition, the global dynamics of the proteins are analysed using the essential-dynamics method. This analysis reveals a slightly higher degree of conservation in dynamics for the three proteins which are functionally related. Both the global and local analyses illustrate how nature has optimized and conserved protein motions for specific biological activity within the ubiquitin family.

Global and Local Fluctuations in Distributions from Ultra-Relativistic Heavy-Ion Interactions

1990 ◽  
Vol T32 ◽  
pp. 147-149
Author(s):  
J Idh ◽  
R Albrecht ◽  
T C Awes ◽  
C Baktash ◽  
P Beckmann ◽  
...  
Keyword(s):  
Heavy Ion ◽  
Ion Interactions ◽  
Local Fluctuations ◽  
Global And Local

A Nonlinear Dynamic Substructuring Approach to Global Dynamics of Flexible Riser Systems

2014 ◽  
Author(s):  
Arya Majed ◽  
Phil Cooper
Keyword(s):  
Dynamic Analysis ◽  
Nonlinear Dynamic ◽  
Nonlinear Dynamic Analysis ◽  
Nonlinear Effects ◽  
Global Dynamics ◽  
Computationally Efficient ◽  
Flexible Riser ◽  
Dynamic Simulations ◽  
Stick Slip ◽  
Global Dynamic

Standard riser global dynamic analysis software packages utilize line element models that cannot capture the complex behavior of flexible risers. This paper presents a computationally efficient nonlinear dynamic analysis methodology capable of incorporating detailed finite element models and scalable to global dynamic simulations of entire flexible riser systems. Subject methodology captures the global geometric nonlinear effects and its coupling to stick-slip friction — a clear requirement for accurate armour stress predictions. In addition, the method enables the formulation of stress transformation matrices which allow the direct recovery of armour stresses from the global simulations. A demonstration problem involving the nonlinear dynamic simulation of a 500m flexible riser system is presented.

VIBRATION ANALYSIS OF A GRAPHENE NANORIBBON UNDER HARMONIC LORENTZ FORCE USING A HYBRID MODAL-MOLECULAR DYNAMICS METHOD

2014 ◽  
Vol 14 (02) ◽  
pp. 1350057 ◽  
Author(s):  
R. D. FIROUZ-ABADI ◽  
H. MOHAMMADKHANI ◽  
H. AMINI
Keyword(s):  
Molecular Dynamics ◽  
Vibration Analysis ◽  
Large Scale ◽  
Nonlinear Vibrations ◽  
Graphene Nanoribbon ◽  
Molecular Dynamics Method ◽  
Dynamic Simulations ◽  
Resonance Frequencies ◽  
Dynamics Method ◽  
Good Agreement

An efficient hybrid modal-molecular dynamics method is developed for the vibration analysis of large scale nanostructures. Using the reduced order method, presented in this paper, linear and nonlinear vibrations of a suspended graphene nanoribbon (GNR) carrying an electric current in a harmonic magnetic field are investigated. The resonance frequencies as well as the nonlinear vibration response obtained by the present technique and direct molecular dynamic simulations are in very good agreement. Also, the obtained results illustrate the hardening behavior of nonlinear vibrations which is diminished by stretching the GNR.

scholarly journals Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Daniel A Keedy ◽  
Lillian R Kenner ◽  
Matthew Warkentin ◽  
Rahel A Woldeyes ◽  
Jesse B Hopkins ◽  
...  
Keyword(s):  
Active Site ◽  
Protein Function ◽  
Conformational Ensemble ◽  
Conformational Heterogeneity ◽  
Time Resolved ◽  
Protein Motions ◽  
Catalytic Function ◽  
Temperature Dependences ◽  
Site Network ◽  
Response To Temperature

Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for structural biology. Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A (CypA) has been previously linked to its catalytic function, but the extent to which the different conformations of these residues are correlated is unclear. Here we compare the conformational ensembles of CypA by multitemperature synchrotron crystallography and fixed-target X-ray free-electron laser (XFEL) crystallography. The diffraction-before-destruction nature of XFEL experiments provides a radiation-damage-free view of the functionally important alternative conformations of CypA, confirming earlier synchrotron-based results. We monitored the temperature dependences of these alternative conformations with eight synchrotron datasets spanning 100-310 K. Multiconformer models show that many alternative conformations in CypA are populated only at 240 K and above, yet others remain populated or become populated at 180 K and below. These results point to a complex evolution of conformational heterogeneity between 180-–240 K that involves both thermal deactivation and solvent-driven arrest of protein motions in the crystal. The lack of a single shared conformational response to temperature within the dynamic active-site network provides evidence for a conformation shuffling model, in which exchange between rotamer states of a large aromatic ring in the middle of the network shifts the conformational ensemble for the other residues in the network. Together, our multitemperature analyses and XFEL data motivate a new generation of temperature- and time-resolved experiments to structurally characterize the dynamic underpinnings of protein function.

scholarly journals Cholesterol sensing by CD81 is important for hepatitis C virus entry

2019 ◽  
Author(s):  
Machaela Palor ◽  
Lenka Stejskal ◽  
Piya Mandal ◽  
Annasara Lenman ◽  
Pia Maria Alberione ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Function ◽  
Binding Pocket ◽  
Receptor Activity ◽  
Conformational Switching ◽  
Dynamic Simulations ◽  
Molecular Scaffold ◽  
Health And Disease ◽  
Cholesterol Binding

CD81 plays a central role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational opening of the large extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol sensing mechanism; however, the relevance of this for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus (HCV). Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81-cholesterol association, but had disparate effects on HCV entry, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified a potential allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol unbound) or closed (cholesterol bound) conformation. The open mutant of CD81 exhibited reduced receptor activity whereas the closed mutant enhanced activity. These data are consistent with CD81 cholesterol sensing resulting in a switch between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81-partner protein networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry and CD81’s function as a molecular scaffold; these insights are relevant to CD81’s varied roles in both health and disease.

scholarly journals Observer Design for Nonlinear Invertible System from the View of Both Local and Global Levels

2020 ◽  
Vol 10 (22) ◽  
pp. 7966
Author(s):  
Mei Zhang ◽  
Qinmu Wu ◽  
Xiangping Chen ◽  
Boutaïeb Dahhou ◽  
Zetao Li
Keyword(s):  
Design Method ◽  
Nonlinear Process ◽  
Observer Design ◽  
Global Dynamics ◽  
State Observation ◽  
System Output ◽  
Interconnected Nonlinear Systems ◽  
Global And Local ◽  
Derivatives Of ◽  
Output Equation

This paper emphasizes the importance of the influences of local dynamics on the global dynamics of a control system. By considering an actuator as an individual, nonlinear subsystem connected with a nonlinear process subsystem in cascade, a structure of interconnected nonlinear systems is proposed which allows for global and local supervision properties of the interconnected systems. To achieve this purpose, a kind of interconnected observer design method is investigated, and the convergence is studied. One major difficulty is that a state observation can only rely on the global system output at the terminal boundary. This is because the connection point between the two subsystems is considered unable to be measured, due to physical or economic reasons. Therefore, the aim of the interconnected observer is to estimate the state vector of each subsystem and the unmeasurable connection point. Specifically, the output used in the observer of the actuator subsystem is replaced by the estimation of the process subsystem observer, while the estimation of this interconnection is treated like an additional state in the observer design of the process subsystem. Expression for this new state is achieved by calculating the derivatives of the output equation of the actuator subsystem. Numerical simulations confirm the effectiveness and robustness of the proposed observer, which highlight the significance of the work compared with state-of-the-art methods.

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