在SARS-CoV-2中对两性HR1的结构和pKa估计:从恒定pHMD的洞察,线性与非线性正常模式分析
Dayanara Lissette Yánez Arcos1, Saravana Prakash Thirumuruganandham1
1Centro de Investigación de Ciencias Humanas y de la Educación (CICHE), Universidad Indoamérica, Ambato 180103, Ecuador.
International journal of molecular sciences
|November 25, 2023
概括
这项研究分析了SARS-CoV-2尖端蛋白.
科学领域:
- *分子动力学和结构生物学
- * 病毒蛋白形状分析.
- * 计算式生物物理学
背景情况:
- *了解病毒蛋白动态对于药物开发至关重要.
- *SARS-CoV-2尖端蛋白的结构变化是细胞进入的关键.
- * 抑制剂结合会影响尖端蛋白的行为.
研究的目的:
- * 为了研究SARS-CoV-2尖端蛋白的结构动态.
- * 关联主要组件分析 (PCA) 和异型网络模型 (ANM) 模式.
- *分析pH值和突变对HR1稳定性和疏水相互作用的影响.
主要方法:
- *对131个A链结构进行主要成分分析 (PCA).
- *线性和非线性正常模式分析 (NMA).
- * 恒定pH分子动力学 (cpH-MD) 模拟和pKa的确定.
- * 疏水性相互作用分析.
主要成果:
- *PCA和ANM模式显示强烈的相关性,验证低频模式.
- * 非线性NMA显示出比线性NMA更大的稳定性和更低的能量需求,以适应形状变化.
- *cpH-MD模拟预测pH依赖的转变,并确定HR1突变的特定pKa值.
- * 疏水性分析提供了对脂质环境中的蛋白质行为的洞察.
结论:
- *低频模式在功能上对尖端蛋白适应抑制剂具有重要意义.
- * 非线性NMA为结构分析提供了更稳定,更节能的模型.
- *pH和特定突变显著改变尖端蛋白的结构和稳定性,影响病毒的进入.
- *了解这些动态对于开发有效的抗病毒策略至关重要.
相关概念视频
Henderson-Hasselbalch Equation
69.2K
The ionization-constant expression for a solution of a weak acid can be written as:
69.2K
Composition of Polyprotic Acid Solutions as a Function of pH
522
Polyprotic acids of the type H2M constitute two ionizable protons. As a result, on titration with a base, they exhibit two equivalence points in the titration curve. During titration, the species H2M, HM−, and M2− will be present in the solution at different points. The fractions of H2M, HM−, and M2− present at the various instances of the titration are denoted by α0, α1, and α2, respectively.
A graph with the alpha values is plotted against the volume of...
A graph with the alpha values is plotted against the volume of...
522
Extraction: Effects of pH
498
Consider a neutral form of an amine, B, with a partition coefficient, K, in a liquid mixture containing organic and aqueous phases. The pH of the aqueous phase affects the charge on acidic and basic solutes, and the charged form is usually more soluble in the aqueous phase. Suppose the conjugate acid form of the amine is soluble only in the aqueous phase while the base form is soluble in both phases. Then the distribution coefficient, D, can be given as the ratio of amine concentration in the...
498
pH Scale
69.0K
Hydronium and hydroxide ions are present both in pure water and in all aqueous solutions, and their concentrations are inversely proportional as determined by the ion product of water (Kw). The concentrations of these ions in a solution are often critical determinants of the solution’s properties and the chemical behaviors of its other solutes. Two different solutions can differ in their hydronium or hydroxide ion concentrations by a million, billion, or even trillion times. A common means of...
69.0K
Polyprotic Acids
29.2K
Acids are classified by the number of protons per molecule that they can give up in a reaction. Acids such as HCl, HNO3, and HCN that contain one ionizable hydrogen atom in each molecule are called monoprotic acids. Their reactions with water are:
29.2K
Acid and Bases: Ka, pKa, and Relative Strengths
26.7K
This lesson delves into a critical aspect of the relative strengths of acids and bases. The strength of an acid is evaluated by the acid dissociation into its conjugate base and a hydronium ion in water. The complete dissociation of a strong acid is confirmed with a very high concentration of hydronium ions. As a result, an incomplete dissociation process affirms a weak acid. Therefore, the equilibrium is in the forward direction for strong acids and backward for weak acids in these reactions.
26.7K


