scholarly journals Computation of conformational transitions in proteins by virtual atom molecular mechanics as validated in application to adenylate kinase

2009 ◽  
Vol 106 (37) ◽  
pp. 15673-15678 ◽  
Author(s):  
Anil Korkut ◽  
Wayne A. Hendrickson
Keyword(s):  
Molecular Mechanics ◽  
Conformational Changes ◽  
Adenylate Kinase ◽  
Normal Modes ◽  
Conformational Transitions ◽  
The Other ◽  
Coarse Grained ◽  
Knowledge Based ◽  
Comprehensive Knowledge ◽  
Transition Pathways

Many proteins function through conformational transitions between structurally disparate states, and there is a need to explore transition pathways between experimentally accessible states by computation. The sizes of systems of interest and the scale of conformational changes are often beyond the scope of full atomic models, but appropriate coarse-grained approaches can capture significant features. We have designed a comprehensive knowledge-based potential function based on a Cα representation for proteins that we call the virtual atom molecular mechanics (VAMM) force field. Here, we describe an algorithm for using the VAMM potential to describe conformational transitions, and we validate this algorithm in application to a transition between open and closed states of adenylate kinase (ADK). The VAMM algorithm computes normal modes for each state and iteratively moves each structure toward the other through a series of intermediates. The move from each side at each step is taken along that normal mode showing greatest engagement with the other state. The process continues to convergence of terminal intermediates to within a defined limit—here, a root-mean-square deviation of 1 Å. Validations show that the VAMM algorithm is highly effective, and the transition pathways examined for ADK are compatible with other structural and biophysical information. We expect that the VAMM algorithm can address many biological systems.

scholarly journals A force field for virtual atom molecular mechanics of proteins

2009 ◽  
Vol 106 (37) ◽  
pp. 15667-15672 ◽  
Author(s):  
Anil Korkut ◽  
Wayne A. Hendrickson
Keyword(s):  
Force Field ◽  
Molecular Mechanics ◽  
Normal Mode ◽  
Conformational Changes ◽  
Normal Mode Analysis ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Biological Macromolecules ◽  
Molecular Mechanics Calculations ◽  
Low Degrees

Activities of many biological macromolecules involve large conformational transitions for which crystallography can specify atomic details of alternative end states, but the course of transitions is often beyond the reach of computations based on full-atomic potential functions. We have developed a coarse-grained force field for molecular mechanics calculations based on the virtual interactions of Cα atoms in protein molecules. This force field is parameterized based on the statistical distribution of the energy terms extracted from crystallographic data, and it is formulated to capture features dependent on secondary structure and on residue-specific contact information. The resulting force field is applied to energy minimization and normal mode analysis of several proteins. We find robust convergence in minimizations to low energies and energy gradients with low degrees of structural distortion, and atomic fluctuations calculated from the normal mode analyses correlate well with the experimental B-factors obtained from high-resolution crystal structures. These findings suggest that the virtual atom force field is a suitable tool for various molecular mechanics applications on large macromolecular systems undergoing large conformational changes.

Allosteric Conformational Transition in Adenylate Kinase: Dynamic Correlations and Implication for Allostery

2010 ◽  
Vol 63 (3) ◽  
pp. 405 ◽  
Author(s):  
Ming S. Liu ◽  
Billy D. Todd ◽  
Richard J. Sadus
Keyword(s):  
Normal Mode ◽  
Conformational Changes ◽  
Adenylate Kinase ◽  
Conformational Transition ◽  
Normal Mode Analysis ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Elastic Network Model ◽  
Protein Functions ◽  
Correlated Motion

An essential aspect of protein science is to determine the deductive relationship between structure, dynamics, and various sets of functions. The role of dynamics is currently challenging our understanding of protein functions, both experimentally and theoretically. To verify the internal fluctuations and dynamics correlations in an enzyme protein undergoing conformational transitions, we have applied a coarse-grained dynamics algorithm using the elastic network model for adenylate kinase. Normal mode analysis reveals possible dynamical and allosteric pathways for the transition between the open and the closed states of adenylate kinase. As the ligands binding induces significant flexibility changes of the nucleotides monophosphate (NMP) domain and adenosine triphosphate (ATP) domain, the diagonalized correlation between different structural transition states shows that most correlated motions occur between the NMP domain and the helices surrounding the ATP domain. The simultaneous existence of positive and negative correlations indicates that the conformational changes of adenylate kinase take place in an allosteric manner. Analyses of the cumulated normal mode overlap coefficients and long-range correlated motion provide new insights of operating mechanisms and dynamics of adenylate kinase. They also suggest a quantitative dynamics criterion for determining the allosteric cooperativity, which may be applicable to other proteins.

scholarly journals A coarse-grained model of the expansion of the human rhinovirus 2 capsid reveals insights in genome release

2019 ◽  
Vol 16 (157) ◽  
pp. 20190044 ◽  
Author(s):  
Giuliana Indelicato ◽  
Paolo Cermelli ◽  
Reidun Twarock
Keyword(s):  
Conformational Changes ◽  
Minimum Energy ◽  
Human Rhinovirus ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Transition Pathways ◽  
Causative Agents ◽  
The Common ◽  
Minimum Energy Paths

Human rhinoviruses are causative agents of the common cold. In order to release their RNA genome into the host during a viral infection, these small viruses must undergo conformational changes in their capsids, whose detailed mechanism is strictly related to the process of RNA extrusion, which has been only partially elucidated. We study here a mathematical model for the structural transition between the native particle of human rhinovirus type 2 and its expanded form, viewing the process as an energy cascade, i.e. a sequence of metastable states with decreasing energy connected by minimum energy paths. We explore several transition pathways and discuss their implications for the RNA exit process.

The Alteration of the Pore Spaces in Sandstones

1973 ◽  
Vol 31 ◽  
pp. 210-211
Author(s):  
R. E. Ferrell ◽  
G. G. Paulson
Keyword(s):  
Electron Microscope ◽  
Scanning Electron Microscope ◽  
The Other ◽  
Coarse Grained ◽  
Depositional Fabric ◽  
Soluble Components ◽  
Scanning Electron ◽  
Shape And Size

The pore spaces in sandstones are the result of the original depositional fabric and the degree of post-depositional alteration that the rock has experienced. The largest pore volumes are present in coarse-grained, well-sorted materials with high sphericity. The chief mechanisms which alter the shape and size of the pores are precipitation of cementing agents and the dissolution of soluble components. Each process may operate alone or in combination with the other, or there may be several generations of cementation and solution.The scanning electron microscope has ‘been used in this study to reveal the morphology of the pore spaces in a variety of moderate porosity, orthoquartzites.

On the Origin of the Microscystalline Structure in Rapidly Solidified IN-100 Powder

1977 ◽  
Vol 35 ◽  
pp. 260-261
Author(s):  
J. M. Walsh ◽  
K. P. Gumz ◽  
J. C. Whittles ◽  
B. H. Kear
Keyword(s):  
The Other ◽  
Coarse Grained ◽  
Microcrystalline Structure ◽  
Routine Examination ◽  
Atomization Process ◽  
Centrifugal Atomization ◽  
Splat Quenching ◽  
Powder Particles ◽  
Dendritic Microstructures ◽  
Rapidly Solidified

During a routine examination of the microstructure of rapidly solidified IN-100 powder, produced by a newly-developed centrifugal atomization process1, essentially two distinct types of microstructure were identified. When a high melt superheat is maintained during atomization, the powder particles are predominantly coarse-grained, equiaxed or columnar, with distinctly dendritic microstructures, Figs, la and 4a. On the other hand, when the melt superheat is reduced by increasing the heat flow to the disc of the rotary atomizer, the powder particles are predominantly microcrystalline in character, with typically one dendrite per grain, Figs, lb and 4b. In what follows, evidence is presented that strongly supports the view that the unusual microcrystalline structure has its origin in dendrite erosion occurring in a 'mushy zone' of dynamic solidification on the disc of the rotary atomizer.The critical observations were made on atomized material that had undergone 'splat-quenching' on previously solidified, chilled substrate particles.

Investigation and Impact of Knowledge-Based Information on Programming Languages Based on Probabilistic Models

2010 ◽  
Vol 39 ◽  
pp. 436-440
Author(s):  
Zhi Ming Qu
Keyword(s):  
Expert Systems ◽  
Programming Languages ◽  
Probabilistic Models ◽  
Role Playing ◽  
Position Paper ◽  
The Other ◽  
Erasure Coding ◽  
Role Playing Games ◽  
Knowledge Based ◽  
Other Hand

In recent years, much research has been devoted to the refinement of IPv6; on the other hand, few have investigated the confusing unification of interrupts and Internet QoS. In this position paper, it demonstrates the emulation of interrupts. In order to overcome this quagmire, a novel system is presented for the intuitive unification of expert systems and massive multiplayer online role-playing games. It is concluded that erasure coding can be verified to make heterogeneous, interposable, and event-driven, which is proved to be applicable.

Conditional Belief and the Ramsey Test

2002 ◽  
Vol 51 ◽  
pp. 215-232
Author(s):  
Scott Sturgeon
Keyword(s):  
Everyday Life ◽  
Common Sense ◽  
The Other ◽  
Coarse Grained ◽  
Degrees Of Belief ◽  
Conditional Belief ◽  
Ramsey Test ◽  
Fine Grained

Consider the frameS believes that—.Fill it with a conditional, sayIf you eat an Apple, you'll drink a Coke.what makes the result true? More generally, what facts are marked by instances ofS believes (A→C)?In a sense the answer is obious: beliefs are so marked. Yet that bromide leads directly to competing schools of thought. And the reason is simple.Common-sense thinks of belief two ways. Sometimes it sees it as a three-part affair. When so viewed either you believe, disbelieve, or suspend judgment. This take on belief is coarse-grained. It says belief has three flavours: acceptance, rejection, neither. But it's not the only way common-sense thinks of belief. Sometimes it's more subtle: ‘How strong is your faith?’ can be apposite between believers. That signals an important fact. Ordinary practice also treats belief as a fine-grained affair. It speaks of levels of confidence. It admits degrees of belief. It contains a fine-grained take as well. There are two ways belief is seen in everyday life. One is coarse-grained. The other is fine-grained.

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