相关实验视频

Updated: Jul 25, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

自由能量扰动对SARS-CoV-2的突变效应的计算 RBD::ACE2结合亲和力

Alina P Sergeeva¹, Phinikoula S Katsamba², Junzhuo Liao³

¹Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: https://twitter.com/AlinaSergeeva.

Journal of molecular biology

|June 24, 2023

概括

计算的自由能量扰动 (FEP) 计算准确地预测了SARS-CoV-2突变中的突变如何激增蛋白质.

科学领域:

病毒学和分子生物学
计算化学计算化学
结构生物学结构生物学

背景情况:

在SARS-CoV-2尖端蛋白的受体结合域 (RBD) 和人类血管素转化酶2 (ACE2) 之间的结合亲缘关系影响病毒的传播能力.
在感染个体中经常观察到特定的RBD突变,可能会改变这种结合相互作用.

研究的目的:

为了研究特定的RBD突变对ACE2结合亲缘关系的影响.
将自由能量扰动 (FEP) 计算的预测精度与实验数据和其他计算方法进行比较.

主要方法:

表面等离子体共振 (SPR) 测量被用于实验性地确定结合亲和关系.
运用自由能量扰动 (FEP) 计算来计算模拟结合亲和力变化.
将SPR结果与现有文献进行比较,并注意到由于实验变化的差异.

主要成果:

SPR结果通常与先前的研究一致,尽管实验变异可能导致差异.
与其他计算方法相比,自由能量扰动 (FEP) 计算显示出更高的性能.
FEP成功预测了稳定突变,并解释了在Omicron变体 (Q498R N501Y双突变) 中观察到的合作稳定.

结论:

自由能量扰动 (FEP) 的计算提供了一种可靠的方法来了解突变对蛋白质-蛋白质结合亲和力的影响.
尽管计算成本高,但FEP对于优化中和抗体等应用来说是一个有价值的工具.
这项研究为在Omicron变体中观察到的结合稳定提供了一个物理机制.

关键词:

在FEPEP中,FEP是FEP.在SPR中使用SPR.ddG 预测的预测蛋白质蛋白质相互作用受体结合域和血管素转化酶2的受体结合域

更多相关视频

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Published on: December 9, 2022

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

相关概念视频

The Equilibrium Binding Constant and Binding Strength

The Equilibrium Binding Constant and Binding Strength

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:

Calculating Standard Free Energy Changes

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...