Jove
Visualize
Contáctanos
JoVE
x logofacebook logolinkedin logoyoutube logo
ACERCA DE JoVE
Visión GeneralLiderazgoBlogCentro de Ayuda JoVE
AUTORES
Proceso de PublicaciónConsejo EditorialAlcance y PolíticasRevisión por ParesPreguntas FrecuentesEnviar
BIBLIOTECARIOS
TestimoniosSuscripcionesAccesoRecursosConsejo Asesor de BibliotecasPreguntas Frecuentes
INVESTIGACIÓN
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchivo
EDUCACIÓN
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualCentro de Recursos para ProfesoresSitio de Profesores
Términos y Condiciones de Uso
Política de Privacidad
Políticas

Videos de Conceptos Relacionados

The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

13.4K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
13.4K
Calculating Standard Free Energy Changes02:49

Calculating Standard Free Energy Changes

22.0K
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...
22.0K
Gibbs Free Energy02:39

Gibbs Free Energy

34.3K
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...
34.3K
Gibbs Free Energy and Thermodynamic Favorability02:23

Gibbs Free Energy and Thermodynamic Favorability

7.0K
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:
7.0K
Free Energy Changes for Nonstandard States03:25

Free Energy Changes for Nonstandard States

11.6K
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:
 
where R is the gas constant (8.314 J/K·mol), T is the absolute temperature in kelvin, and Q is the reaction quotient. This equation may be used to predict the spontaneity of a process under any given set of conditions.
Reaction Quotient...
11.6K
Enzymes and Activation Energy01:13

Enzymes and Activation Energy

12.5K
The activation energy (or free energy of activation), abbreviated as Ea, is the small amount of energy input necessary for all chemical reactions to occur. During chemical reactions, certain chemical bonds break, and new ones form. For example, when a glucose molecule breaks down, bonds between the molecule's carbon atoms break. Since these are energy-storing bonds, they release energy when broken. However, the molecule must be somewhat contorted to get into a state that allows the bonds to...
12.5K

También podría leer

Artículos Relacionados

Artículos vinculados a este trabajo por autores compartidos, revista y gráfico de citas.

Ordenar por
Same author

Boltz-ABFE: Free Energy Perturbation without Crystal Structures.

Journal of chemical theory and computation·2026
Same author

Repeatability of Relative Free Energy Calculations in Solution with ANI-2x and MACE-OFF23.

Journal of chemical theory and computation·2025
Same author

Architecture-Independent Absolute Solvation Free Energy Calculations with Neural Network Potentials.

The journal of physical chemistry letters·2025
Same author

Transferable Neural Network Potentials and Condensed Phase Properties.

Journal of chemical information and modeling·2025
Same author

Basic Stability Tests of Machine Learning Potentials for Molecular Simulations in Computational Drug Discovery.

Journal of chemical information and modeling·2025
Same author

alchemlyb: the simple alchemistry library.

Journal of open source software·2025
Same journal

Complementing Onsager's Conductivity Theory by Grotthuss Mechanism Mitigation via Ion-Induced Depletion of Hydrogen-Bond-Donating Water.

Journal of chemical theory and computation·2026
Same journal

Microscopic Stress in Biomembranes: A Perspective on Key Concepts, Methods, and Applications.

Journal of chemical theory and computation·2026
Same journal

Analytic Nuclear Gradients Including Oriented External Electric Fields in a Molecule-Fixed Frame.

Journal of chemical theory and computation·2026
Same journal

Knowledge Distillation of a Protein Language Model Yields a Foundational Implicit Solvent Model.

Journal of chemical theory and computation·2026
Same journal

Generalizable Protein Folding Pathway Exploration with DA2-GRASP: Extending Beyond Miniproteins.

Journal of chemical theory and computation·2026
Same journal

Improving PCM in Protic Media: Markov State Models for TD-DFT Calculations.

Journal of chemical theory and computation·2026
Ver todos los artículos relacionados

Video Experimental Relacionado

Updated: Sep 10, 2025

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
05:51

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Published on: July 19, 2019

6.3K

Optimización de los cálculos de energía libre absolutamente vinculantes para el uso de la producción

Zhiyi Wu1, Gerhard Konig1, Stefan Boresch2

  • 1Recursion, Schrodinger Building, Oxford OX4 4GE, U.K.

Journal of chemical theory and computation
|August 27, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Los cálculos optimizados de la energía libre absoluta de unión alquímica (ABFE) mejoran la predicción de la afinidad de unión proteína-ligando. Los nuevos protocolos mejoran la estabilidad de la simulación y la convergencia para el descubrimiento de fármacos, reduciendo los errores en los cálculos de energía libre.

Más Videos Relacionados

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.1K
Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
06:24

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology

Published on: December 15, 2017

10.2K

Videos de Experimentos Relacionados

Last Updated: Sep 10, 2025

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
05:51

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Published on: July 19, 2019

6.3K
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.1K
Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
06:24

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology

Published on: December 15, 2017

10.2K

Área de la Ciencia:

  • Química computacional
  • Descubrimiento de drogas
  • Modelado molecular

Sus antecedentes:

  • La predicción de la afinidad de unión proteína-ligando es crucial para el descubrimiento de fármacos de moléculas pequeñas.
  • Los cálculos de la energía libre absoluta de enlace alquímico (ABFE) son precisos, pero pueden sufrir de inestabilidad y poca convergencia en proyectos a gran escala.

Objetivo del estudio:

  • Optimizar el protocolo ABFE para mejorar la estabilidad, la convergencia y la precisión en la predicción de la afinidad de unión proteína-ligando.
  • Abordar las limitaciones de los métodos ABFE actuales en las tuberías de descubrimiento de fármacos a gran escala.

Principales métodos:

  • Desarrolló un nuevo algoritmo para la selección de restricción de la postura de la proteína-ligando, incorporando datos de enlaces de hidrógeno para evitar inestabilidades numéricas y mejorar la convergencia.
  • Optimizado el protocolo de aniquilación para minimizar el error de energía libre.
  • Reordenó la escala de las interacciones (electrostática, Lennard-Jones, restricciones, torsiones intramoleculares) para mejorar sistemáticamente la precisión.

Principales resultados:

  • El protocolo ABFE optimizado demostró variaciones significativamente más bajas en los resultados de energía libre en cuatro sistemas de referencia (TYK2, P38, JNK1, CDK2).
  • Se han logrado mejoras de hasta 0,23 kcal/mol en el error de la raíz media cuadrada en comparación con el protocolo original.
  • Las modificaciones condujeron a simulaciones más estables y confiables.

Conclusiones:

  • Las optimizaciones implementadas mejoran sustancialmente la precisión y fiabilidad de los cálculos alquímicos de ABFE para la predicción de la afinidad de unión de proteínas y ligandos.
  • Estos protocolos mejorados ofrecen una herramienta más robusta para el descubrimiento computacional de fármacos, lo que permite una selección más eficiente de posibles fármacos candidatos.