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Related Concept Videos

Free Energy Changes for Nonstandard States03:25

Free Energy Changes for Nonstandard States

The free energy change for a process taking place with reactants and products present under nonstandard conditions (pressures other than 1 bar; concentrations other than 1 M) is related to the standard free energy change according to this equation:
Gibbs Free Energy02:39

Gibbs Free Energy

One of the challenges of using the second law of thermodynamics to determine if a process is spontaneous is that it requires measurements of the entropy change for the system and the entropy change for the surroundings. An alternative approach involving a new thermodynamic property defined in terms of system properties only was introduced in the late nineteenth century by American mathematician Josiah Willard Gibbs. This new property is called the Gibbs free energy (G) (or simply the free...
Calculating Standard Free Energy Changes02:49

Calculating Standard Free Energy Changes

The free energy change for a reaction that occurs under the standard conditions of 1 bar pressure and at 298 K is called the standard free energy change. Since free energy is a state function, its value depends only on the conditions of the initial and final states of the system. A convenient and common approach to the calculation of free energy changes for physical and chemical reactions is by use of widely available compilations of standard state thermodynamic data. One method involves the...
Entropy02:39

Entropy

Salt particles that have dissolved in water never spontaneously come back together in solution to reform solid particles. Moreover, a gas that has expanded in a vacuum remains dispersed and never spontaneously reassembles. The unidirectional nature of these phenomena is the result of a thermodynamic state function called entropy (S). Entropy is the measure of the extent to which the energy is dispersed throughout a system, or in other words, it is proportional to the degree of disorder of a...
Entropy01:18

Entropy

The first law of thermodynamics is quantitatively formulated via an equation relating the internal energy of a system, the heat exchanged by it, and the work done on it. A quantitative formulation of the second law of thermodynamics leads to defining a state function, the entropy.
When an ideal gas expands isothermally, the disorder in the gas increases. From the molecular perspective, the gas molecules have more volume to move around in.
Consider an infinitesimal step in the expansion, which...
Effects of Temperature on Free Energy02:11

Effects of Temperature on Free Energy

The spontaneity of a process depends upon the temperature of the system. Phase transitions, for example, will proceed spontaneously in one direction or the other depending upon the temperature of the substance in question. Likewise, some chemical reactions can also exhibit temperature-dependent spontaneities. To illustrate this concept, the equation relating free energy change to the enthalpy and entropy changes for the process is considered:

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High-Pressure NMR Experiments for Detecting Protein Low-Lying Conformational States
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Free-energy differences between states with different conformational ensembles.

Jose Antonio Garate1, Chris Oostenbrink

  • 1Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Vienna, Austria.

Journal of Computational Chemistry
|March 26, 2013
PubMed
Summary

This study introduces a new method, thermodynamic integration with local elevation umbrella sampling (TI-LE/US), to improve free-energy calculations for molecules with high-energy barriers. The enhanced sampling technique successfully calculated conformational free energies for guanosine triphosphate analogs.

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Area of Science:

  • Computational chemistry
  • Molecular modeling
  • Biophysical chemistry

Background:

  • Accurate free-energy calculations are crucial for understanding molecular behavior.
  • High-energy barriers between molecular conformations pose significant sampling challenges.
  • Alchemical free-energy calculations require efficient methods to overcome these barriers.

Purpose of the Study:

  • To present and validate a novel enhanced sampling technique, thermodynamic integration with local elevation umbrella sampling (TI-LE/US).
  • To improve convergence and reliability in alchemical free-energy calculations for systems with high-energy barriers.
  • To compute conformational free energies for guanosine triphosphate (GTP) and its analogs.

Main Methods:

  • Application of thermodynamic integration (TI) combined with local elevation umbrella sampling (LE/US).
  • Utilized the guanosine triphosphate (GTP) to 8-Br-GTP perturbation system, known for high-energy barriers.
  • Compared TI-LE/US results with the enhanced-sampling one-step perturbation (OSP) method for validation.

Main Results:

  • TI-LE/US significantly improved sampling convergence along the reaction coordinate.
  • Linear interpolation of end-state biasing potentials was effective in enhancing sampling.
  • Conformational free-energy differences for syn and anti states of GTP analogs were successfully computed.

Conclusions:

  • TI-LE/US offers a robust and reliable approach for alchemical free-energy calculations involving high-energy barriers.
  • The method provides accurate conformational free energies, comparable to experimental and theoretical data.
  • Coupled OSP with LE/US enables calculation of both conformational and alchemical free energies for GTP analogs.