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関連する概念動画

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

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関連する実験動画

Updated: Sep 10, 2025

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

Published on: July 19, 2019

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生産利用のための絶対的拘束力のある自由エネルギー計算の最適化

Zhiyi Wu1, Gerhard Konig1, Stefan Boresch2

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

Journal of chemical theory and computation
|August 27, 2025
PubMed
まとめ
この要約は機械生成です。

最適化された化学的絶対結合自由エネルギー (ABFE) 計算により,タンパク質-リガンド結合親和の予測が改善されます. 新しいプロトコルは,シミュレーションの安定性と薬剤発見の収束性を高め,自由エネルギー計算の誤差を軽減します.

さらに関連する動画

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

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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

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関連する実験動画

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

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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

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科学分野:

  • コンピュータ化学
  • 薬物の発見
  • 分子モデリング

背景:

  • タンパク質-リガンド結合の親和性予測は,小分子薬の発見に不可欠である.
  • アルケミカル絶対結合自由エネルギー (ABFE) の計算は正確ですが,大規模なプロジェクトでは不安定で収束が悪いことがあります.

研究 の 目的:

  • ABFEプロトコルを最適化して,タンパク質-リガンド結合親和性予測の安定性,収束性,精度を向上させる.
  • 大規模な薬剤発見のパイプラインにおける現在の ABFE 方法の限界に対処する.

主な方法:

  • タンパク質-リガンドポーズ抑制選択のための新しいアルゴリズムを開発し,数値の不安定性を防止し,収束を改善するために水素結合データを組み込みました.
  • 破壊プロトコルを最適化して 自由エネルギーエラーを最小限にしました
  • 相互作用のスケーリング (静電学,レナード・ジョーンズ,拘束,分子内トルション) を再編成し,精度を体系的に向上させた.

主要な成果:

  • 最適化されたABFEプロトコルは,4つのベンチマークシステム (TYK2,P38,JNK1,CDK2) で自由エネルギー結果の相違が著しく低いことを示した.
  • 初期プロトコルと比較して,平方根平均誤差で0. 23kcal/molまでの改善を達成しました.
  • 改造により,より安定した,信頼性の高いシミュレーションが可能になった.

結論:

  • 実施された最適化は,タンパク質-リガンド結合親和性予測のための錬金術的ABFE計算の正確性,精度,および信頼性を大幅に改善します.
  • これらの強化されたプロトコルは,潜在的な薬剤候補のより効率的なスクリーニングを可能にする,コンピュータによる薬剤発見のためのより堅牢なツールを提供します.