Maximum Flux Transition Paths of Conformational Change
Ruijun Zhao1, Juanfang Shen, Robert D Skeel
1Department of Computer Science, Purdue University, West Lafayette, IN, 47907-2107.
Journal of Chemical Theory and Computation
|October 5, 2010
Summary
Calculating biomolecular transition paths between states A and B is simplified using committor functions. This method identifies the maximum flux transition path, offering a robust computational approach for complex systems.
Area of Science:
- Biomolecular systems
- Computational chemistry
- Statistical mechanics
Background:
- Understanding transitions between metastable states (A and B) in biomolecular systems is crucial.
- Existing methods for calculating transition paths can be computationally intensive and complex.
- Reduced sets of collective variables are often used to simplify path calculations.
Purpose of the Study:
- To develop a more informative and manageable method for calculating likely transition paths between biomolecular states.
- To define and compute the "center" of clustered trajectories in collective variable space.
- To introduce a novel path definition based on the committor function and maximum flux.
Main Methods:
- Utilizing the committor function to define isocommittors, which "foliate" the transition region.
- Defining the maximum flux transition path based on the highest crossing rate of reactive trajectories across isocommittors.
- Introducing three approximations to yield a tractable, nonsingular two-point boundary-value problem.
- Developing a simple and robust algorithm to solve the boundary-value problem.
Main Results:
- The proposed maximum flux transition path is invariant to coordinate changes and uses simpler differential equations.
- This path is argued to be superior to previously proposed paths, with the exception of the finite-temperature string method path.
- The method results in a solvable nonsingular two-point boundary-value problem.
- A robust algorithm for solving this problem has been developed and its performance discussed.
Conclusions:
- The maximum flux transition path, derived from the committor function, provides an efficient and accurate method for studying biomolecular transitions.
- The developed computational approach simplifies complex calculations and offers advantages in coordinate invariance and equation simplicity.
- The method's tractability and the availability of a robust algorithm make it a valuable tool for biomolecular dynamics research.
Related Concept Videos
01:25Transition State Theory
Transition-state theory, also known as activated-complex theory, provides a molecular-level explanation of reaction rates in both gas-phase and solution-phase reactions. It extends earlier kinetic models by considering the formation of a short-lived, high-energy configuration during a reaction.The progress of a chemical reaction can be represented using a reaction profile, which plots potential energy against the reaction coordinate. As two reactant molecules approach one another, their...
01:21Path Between Thermodynamics States
Consider the two thermodynamic processes involving an ideal gas that are represented by paths AC and ABC in Figure 1:
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...