Protein cavities and tunnels are critical for function. Ligand recognition and binding, transport, and enzyme catalysis require cavities rearrangements. Therefore, the flexibility of cavities should be guaranteed by protein vibrational dynamics. Molecular dynamics simulations provide a framework to explore conformational plasticity of protein cavities. Herein, we present a novel procedure to characterize the dynamics of protein cavities in terms of their volume gradient vector. For this purpose, we make use of algorithms for calculation of the cavity volume that result robust for numerical differentiations. Volume gradient vector is expressed in terms of principal component analysis obtained from equilibrated molecular dynamics simulations. We analyze contributions of principal component modes to the volume gradient vector according to their frequency and degree of delocalization. In all our test cases, we find that low frequency modes play a critical role together with minor contributions of high frequency modes. These modes involve concerted motions of significant fractions of the total residues lining the cavities. We make use of variations of the potential energy of a protein in the direction of the volume gradient vector as a measure of flexibility of the cavity. We show that proteins whose collective low frequency fluctuations contribute the most to changes of cavity volume exhibit more flexible cavities.

中文翻译：

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蛋白质波动与腔变化的关系

蛋白质腔和通道对于功能至关重要。配体识别和结合，转运和酶催化需要腔重排。因此，应通过蛋白质振动动力学来确保腔体的柔韧性。分子动力学模拟提供了探索蛋白质腔的构象可塑性的框架。在本文中，我们提出了一种新颖的程序，可以根据其体积梯度向量来表征蛋白腔的动力学。为此，我们利用算法来计算型腔体积，从而对数值微分产生稳健的结果。体积梯度向量用从平衡分子动力学模拟获得的主成分分析表示。我们根据其主频和离域程度分析了主成分模式对体积梯度向量的贡献。在我们所有的测试案例中，我们发现低频模式与高频模式的微小贡献一起起着至关重要的作用。这些模式涉及腔内衬的全部残留物的大部分的协同运动。我们利用在体积梯度矢量方向上蛋白质势能的变化来衡量腔体的柔韧性。我们表明，其集体的低频波动对腔体积的变化贡献最大的蛋白质表现出更灵活的腔。这些模式涉及腔内衬的全部残留物的大部分的协同运动。我们利用在体积梯度矢量方向上蛋白质势能的变化来衡量腔体的柔韧性。我们表明，其集体的低频波动对腔体积的变化贡献最大的蛋白质表现出更灵活的腔。这些模式涉及腔内衬的全部残留物的大部分的协同运动。我们利用在体积梯度矢量方向上蛋白质势能的变化来衡量腔体的柔韧性。我们表明，其集体的低频波动对腔体积的变化贡献最大的蛋白质表现出更灵活的腔。