skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Hierarchical analysis of conformational dynamics in biomolecules: Transition networks of meta-stable states

Journal Article · · The Journal of Chemical Physics
DOI:https://doi.org/10.1063/1.2714539· OSTI ID:932198
 [1];  [2];  [1]; ORCiD logo [3]
  1. Heidelberg University, Germany
  2. Free University of Berlin, Germany
  3. ORNL
+ Show Author Affiliations

Molecular dynamics simulation generates large quantities of data that must be interpreted using physically meaningful analysis. A common approach is to describe the system dynamics in terms of transitions between coarse partitions of conformational space. In contrast to previous work that partitions the space according to geometric proximity, the authors examine here clustering based on kinetics, merging configurational microstates together so as to identify long-lived, i.e., dynamically metastable, states. As test systems microsecond molecular dynamics simulations of the polyalanines Ala{sub 8} and Ala{sub 12} are analyzed. Both systems clearly exhibit metastability, with some kinetically distinct metastable states being geometrically very similar. Using the backbone torsion rotamer pattern to define the microstates, a definition is obtained of metastable states whose lifetimes considerably exceed the memory associated with interstate dynamics, thus allowing the kinetics to be described by a Markov model. This model is shown to be valid by comparison of its predictions with the kinetics obtained directly from the molecular dynamics simulations. In contrast, clustering based on the hydrogen-bonding pattern fails to identify long-lived metastable states or a reliable Markov model. Finally, an approach is proposed to generate a hierarchical model of networks, each having a different number of metastable states. The model hierarchy yields a qualitative understanding of the multiple time and length scales in the dynamics of biomolecules.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-00OR22725
OSTI ID:
932198
Journal Information:
The Journal of Chemical Physics, Vol. 126, Issue 15; ISSN 0021-9606
Country of Publication:
United States
Language:
English

References (44)

Computing Best Transition Pathways in High-Dimensional Dynamical Systems: Application to the Alpha L \leftrightharpoons Beta \leftrightharpoons Alpha R Transitions in Octaalanine journal January 2006
Geometric versus topological clustering: An insight into conformation mapping journal February 1997
Information-Theoretic Measures for Knowledge Discovery and Data Mining book January 2003
Foldamer dynamics expressed via Markov state models. II. State space decomposition journal September 2005
Locally accessible conformations of proteins: Multiple molecular dynamics simulations of crambin journal March 1998
Archetypal energy landscapes: Dynamical diagnosis journal January 2005
Transition Networks for the Comprehensive Characterization of Complex Conformational Change in Proteins journal May 2006
Dynamics of hierarchical folding on energy landscapes of hexapeptides journal January 2001
Exploring the Helix-Coil Transition via All-Atom Equilibrium Ensemble Simulations journal April 2005
Describing Protein Folding Kinetics by Molecular Dynamics Simulations. 1. Theory † journal May 2004
Error analysis and efficient sampling in Markovian state models for molecular dynamics journal November 2005
Essential dynamics of reversible peptide folding: memory-free conformational dynamics governed by internal hydrogen bonds journal May 2001
Energy landscapes, global optimization and dynamics of the polyalanine Ac(ala)8NHMe journal April 2001
Describing Protein Folding Kinetics by Molecular Dynamics Simulations. 2. Example Applications to Alanine Dipeptide and a β-Hairpin Peptide † journal May 2004
Folding of the GB1 hairpin peptide from discrete path sampling journal July 2004
Statistical clustering techniques for the analysis of long molecular dynamics trajectories: analysis of 2.2-ns trajectories of YPGDV journal January 1993
X‐ray scattering in liquid water at pressures of up to 7.7 kbar: Test of a fluctuation model journal January 1994
Metastability of the folded states of globular proteins. journal May 1990
CHARMM: A program for macromolecular energy, minimization, and dynamics calculations journal July 1983
Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics journal April 2007
Reaction path study of conformational transitions in flexible systems: Applications to peptides journal May 1990
The topology of multidimensional potential energy surfaces: Theory and application to peptide structure and kinetics journal January 1997
Protein folding pathways from replica exchange simulations and a kinetic network model journal March 2005
Simulations of Human Lysozyme: Probing the Conformations Triggering Amyloidosis journal April 2003
A Direct Approach to Conformational Dynamics Based on Hybrid Monte Carlo journal May 1999
Topography and Dynamics of Multidimensional Interatomic Potential Surfaces journal May 1995
The free energy landscape and dynamics of met-enkephalin journal November 2003
Extracting Markov Models of Peptide Conformational Dynamics from Simulation Data journal May 2005
Solvent effects on the energy landscapes and folding kinetics of polyalanine journal February 2001
Validation of Markov state models using Shannon’s entropy journal February 2006
Hidden complexity of free energy surfaces for peptide (protein) folding journal October 2004
Automated Model Reduction for Complex Systems Exhibiting Metastability journal January 2006
A strategy for analysis of (molecular) equilibrium simulations: Configuration space density estimation, clustering, and visualization journal February 2001
Using path sampling to build better Markovian state models: Predicting the folding rate and mechanism of a tryptophan zipper beta hairpin journal January 2004
Energy landscapes of conformationally constrained peptides journal January 2001
Generalized correlation for biomolecular dynamics journal December 2005
Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water journal September 2005
Free energy landscapes of model peptides and proteins journal February 2003
Analysis of a complex of statistical variables into principal components. journal January 1933
Stochastic molecular optimization using generalized simulated annealing journal April 1998
Energy landscapes of model polyalanines journal July 2002
Long‐Time Protein Folding Dynamics from Short‐Time Molecular Dynamics Simulations journal January 2006
Identification of almost invariant aggregates in reversible nearly uncoupled Markov chains journal August 2000
Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions journal May 1994

Similar Records

Hierarchical analysis of conformational dynamics in biomolecules: Transition networks of metastable states
Journal Article · Sun Apr 01 00:00:00 EDT 2007 · The Journal of Chemical Physics · OSTI ID:932198
+1 more
On the advantages of exploiting memory in Markov state models for biomolecular dynamics
Journal Article · Tue Jul 07 00:00:00 EDT 2020 · Journal of Chemical Physics · OSTI ID:932198
+2 more
Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides
Journal Article · Tue Mar 22 00:00:00 EDT 2016 · Molecular Simulation · OSTI ID:932198

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
MOLECULAR DYNAMICS METHOD
ALANINES
ORGANIC POLYMERS
KINETICS
METASTABLE STATES
MATHEMATICAL MODELS
BIOLOGICAL MATERIALS