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相关概念视频

The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

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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:
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Calculating Standard Free Energy Changes02:49

Calculating Standard Free Energy Changes

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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...
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Gibbs Free Energy02:39

Gibbs Free Energy

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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...
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Gibbs Free Energy and Thermodynamic Favorability02:23

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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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Free Energy Changes for Nonstandard States03:25

Free Energy Changes for Nonstandard States

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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...
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Enzymes and Activation Energy01:13

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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...
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Updated: Sep 10, 2025

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
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优化生产使用的绝对有约束力的自由能源计算

Zhiyi Wu1, Gerhard Konig1, Stefan Boresch2

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

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|August 27, 2025
PubMed
概括
此摘要是机器生成的。

优化的化学绝对结合自由能量 (ABFE) 计算提高了蛋白质-联体结合亲和度的预测. 新的协议提高了模拟稳定性和药物发现的趋同性,减少了自由能量计算中的错误.

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科学领域:

  • 计算化学
  • 药物发现
  • 分子建模

背景情况:

  • 在小分子药物发现中,蛋白质-连接体结合性预测至关重要.
  • 化学绝对结合自由能量 (ABFE) 的计算是准确的,但在大型项目中可能会出现不稳定性和差距.

研究的目的:

  • 优化 ABFE 协议以提高蛋白质 - 连接物结合性预测的稳定性,收性和精度.
  • 解决目前大规模药物发现管道中的ABFE方法的局限性.

主要方法:

  • 开发了一种新型的蛋白质 - 连接体姿势限制选择算法, 结合键数据以防止数值不稳定性和改善融合.
  • 优化了灭绝协议以最大限度地减少能量错误.
  • 重组了相互作用的缩放 (静电学,莱纳德-斯,束,分子内扭曲) 以系统地提高精度.

主要成果:

  • 优化的ABFE协议在四个基准系统 (TYK2,P38,JNK1,CDK2) 中显示出较低的自由能量结果差异.
  • 与原始方案相比,在平方根平均误差方面取得了高达0. 23kcal/ mol的改善.
  • 这些修改导致了更稳定,更可靠的模拟.

结论:

  • 实施的优化大大提高了蛋白质-结亲和度预测的化学ABFE计算的准确性,精度和可靠性.
  • 这些增强的协议为计算药物发现提供了更强大的工具,使潜在药物候选者的选更有效.