Constructing Kinetic Network Models to Elucidate Mechanisms of Functional Conformational Changes of Enzymes and Their Recognition with Ligands

2016 ◽  
pp. 343-371 ◽  
Author(s):  
L. Zhang ◽  
H. Jiang ◽  
F.K. Sheong ◽  
F. Pardo-Avila ◽  
P.P.-H. Cheung ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Network Models

scholarly journals Coarse-Grained Models Reveal Functional Dynamics - I. Elastic Network Models – Theories, Comparisons and Perspectives

2008 ◽  
Vol 2 ◽  
pp. BBI.S460 ◽  
Author(s):  
Lee-Wei Yang ◽  
Choon-Peng Chng
Keyword(s):  
Conformational Changes ◽  
Conformational Dynamics ◽  
Computational Cost ◽  
Network Models ◽  
Coarse Graining ◽  
Coarse Grained ◽  
Elastic Network ◽  
Elastic Network Models ◽  
Time Space ◽  
Functional Dynamics

In this review, we summarize the progress on coarse-grained elastic network models (CG-ENMs) in the past decade. Theories were formulated to allow study of conformational dynamics in time/space frames of biological interest. Several highlighted models and their underlined hypotheses are introduced in physical depth. Important ENM offshoots, motivated to reproduce experimental data as well as to address the slow-mode-encoded configurational transitions, are also introduced. With the theoretical developments, computational cost is significantly reduced due to simplified potentials and coarse-grained schemes. Accumulating wealth of data suggest that ENMs agree equally well with experiment in describing equilibrium dynamics despite their distinct potentials and levels of coarse-graining. They however do differ in the slowest motional components that are essential to address large conformational changes of functional significance. The difference stems from the dissimilar curvatures of the harmonic energy wells described for each model. We also provide our views on the predictability of ‘open to close’ (open→close) transitions of biomolecules on the basis of conformational selection theory. Lastly, we address the limitations of the ENM formalism which are partially alleviated by the complementary CG-MD approach, to be introduced in the second paper of this two-part series.

scholarly journals Analysis of Nanoconfined Protein Dielectric Signals Using Charged Amino Acid Network Models

2020 ◽  
Vol 73 (8) ◽  
pp. 803
Author(s):  
Lorenza Pacini ◽  
Laetitia Bourgeat ◽  
Anatoli Serghei ◽  
Claire Lesieur
Keyword(s):  
Thermal Treatment ◽  
Conformational Changes ◽  
Protein Function ◽  
Soft Matter ◽  
Dipole Moments ◽  
Network Models ◽  
Integrative Approach ◽  
Network Analyses ◽  
Local Perturbations ◽  
Slow Motions

Protein slow motions involving collective molecular fluctuations on the timescale of microseconds to seconds are difficult to measure and not well understood despite being essential to sustain protein folding and protein function. Broadband dielectric spectroscopy (BDS) is one of the most powerful experimental techniques to monitor, over a broad frequency and temperature range, the molecular dynamics of soft matter through the orientational polarisation of permanent dipole moments that are generated by the chemical structure and morphological organisation of matter. Its typical frequency range goes from 107 Hz down to 10−3 Hz, being thus suitable for investigations on slow motions in proteins. Moreover, BDS has the advantage of providing direct experimental access to molecular fluctuations taking place on different length-scales, from local to cooperative dipolar motions. The unfolding of the cholera toxin B pentamer (CtxB5) after thermal treatment for 3h at 80°C is investigated by BDS under nanoconfined and dehydrated conditions. From the X-ray structure of the toxin pentamer, network-based models are used to infer the toxin dipoles present in the native state and to compute their stability and dielectric properties. Network analyses highlight three domains with distinct dielectric and stability properties that support a model where the toxin unfolds into three conformations after the treatment at 80°C. This novel integrative approach offers some perspective into the investigation of the relation between local perturbations (e.g. mutation, thermal treatment) and larger scale protein conformational changes. It might help ranking protein sequence variants according to their respective scale of dynamics perturbations.

What's in a model? Network models as tools instead of representations of what psychiatric disorders really are

2019 ◽  
Vol 42 ◽  
Author(s):  
Hanna M. van Loo ◽  
Jan-Willem Romeijn
Keyword(s):  
Psychiatric Disorders ◽  
Network Models ◽  
Model Network

AbstractNetwork models block reductionism about psychiatric disorders only if models are interpreted in a realist manner – that is, taken to represent “what psychiatric disorders really are.” A flexible and more instrumentalist view of models is needed to improve our understanding of the heterogeneity and multifactorial character of psychiatric disorders.

Special, radical, failure of reduction in psychiatry

2019 ◽  
Vol 42 ◽  
Author(s):  
Don Ross
Keyword(s):  
Mental Disorder ◽  
Brain Structure ◽  
Causal Structure ◽  
Network Models ◽  
Gambling Addiction ◽  
Brain Disorder ◽  
Mental Processes ◽  
Special Radical ◽  
Intentional Relationships

AbstractUse of network models to identify causal structure typically blocks reduction across the sciences. Entanglement of mental processes with environmental and intentional relationships, as Borsboom et al. argue, makes reduction of psychology to neuroscience particularly implausible. However, in psychiatry, a mental disorder can involve no brain disorder at all, even when the former crucially depends on aspects of brain structure. Gambling addiction constitutes an example.

Influence of Calcium Ions on the Plant Cell Surface: Membrane Fusions and Conformational Changes

1974 ◽  
Vol 32 ◽  
pp. 154-155
Author(s):  
D. James Morré ◽  
Charles E. Bracker ◽  
William J. VanDerWoude
Keyword(s):  
Cell Wall ◽  
Cell Surface ◽  
Conformational Changes ◽  
Calcium Ions ◽  
Surface Membrane ◽  
Carboxyl Groups ◽  
Cross Linking ◽  
Ultrastructural Evidence ◽  
Glycine Max L ◽  
Wall Extensibility

Calcium ions in the concentration range 5-100 mM inhibit auxin-induced cell elongation and wall extensibility of plant stems. Inhibition of wall extensibility requires that the tissue be living; growth inhibition cannot be explained on the basis of cross-linking of carboxyl groups of cell wall uronides by calcium ions. In this study, ultrastructural evidence was sought for an interaction of calcium ions with some component other than the wall at the cell surface of soybean (Glycine max (L.) Merr.) hypocotyls.

Role of spectrin in membrane fusion and in shape change of human erythrocyte ghost

1978 ◽  
Vol 36 (2) ◽  
pp. 328-329
Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston
Keyword(s):  
Conformational Changes ◽  
Human Erythrocyte ◽  
Shape Change ◽  
Membrane Surface ◽  
Slight Modification ◽  
Active Role ◽  
Main Role ◽  
Bank Blood ◽  
Human Erythrocyte Ghost

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.

Pinocytotic-Like Forms of Mitochondria From Rat Anterior Pituitary

1968 ◽  
Vol 26 ◽  
pp. 146-147
Author(s):  
Burton B. Silver
Keyword(s):  
Electron Micrographs ◽  
Conformational Changes ◽  
Anterior Pituitary ◽  
Dynamic State ◽  
Surrounding Cell ◽  
The Matrix ◽  
The Moment ◽  
Cell Medium ◽  
Sectioned Tissue ◽  
State Of Activity

Sectioned tissue rarely indicates evidence of what is probably a highly dynamic state of activity in mitochondria which have been reported to undergo a variety of movements such as streaming, divisions and coalescence. Recently, mitochondria from the rat anterior pituitary have been fixed in a variety of configurations which suggest that conformational changes were occurring at the moment of fixation. Pinocytotic-like vacuoles which may be taking in or expelling materials from the surrounding cell medium, appear to be forming in some of the mitochondria. In some cases, pores extend into the matrix of the mitochondria. In other forms, the remains of what seems to be pinched off vacuoles are evident in the mitochondrial interior. Dense materials, resembling secretory droplets, appear at the junction of the pores and the cytoplasm. The droplets are similar to the secretory materials commonly identified in electron micrographs of the anterior pituitary.

Application of Lattice Imaging Techniques to Amorphous Films

1975 ◽  
Vol 33 ◽  
pp. 8-9
Author(s):  
S. R. Herd ◽  
P. Chaudhari
Keyword(s):  
Nearest Neighbor ◽  
Random Network ◽  
Imaging Techniques ◽  
Network Models ◽  
Accurate Method ◽  
Direct Transmission ◽  
Lattice Imaging ◽  
Transmission Electron ◽  
Lattice Planes ◽  
Nearest Neighbor Distances

Electron diffraction and direct transmission have been used extensively to study the local atomic arrangement in amorphous solids and in particular Ge. Nearest neighbor distances had been calculated from E.D. profiles and the results have been interpreted in terms of the microcrystalline or the random network models. Direct transmission electron microscopy appears the most direct and accurate method to resolve this issue since the spacial resolution of the better instruments are of the order of 3Å. In particular the tilted beam interference method is used regularly to show fringes corresponding to 1.5 to 3Å lattice planes in crystals as resolution tests.

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