Here, we analyze the structural features of a ligand binding domain (LBD) in COVID-19 main protease (MP) followed by the interactions between the inhibitor N3 and MP-LBD residues through the molecular dynamics simulations. The time based changes in physical parameters that includes root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RG), dihedral distributions, residue velocity, radial distribution function (RDF) and H-bonding signify the degrees of folding states in MP-N3 complex formed by the superimposed b-barrels and flexible a-helices. Sharp and flat RDF peaks observed for the atom pairs dictate the flexibility of MP-LBD residues during their interactions with N3. In spite of larger solvent accessibility of N3, it interacts strongly with the LBD residues resulting in H-bonding. Among the LBD residues, GLU166 is found to have the lowest residue velocity that offers the sharp RDF peaks for three H-bonding atom pairs nearly at 2 Å radial distance, whereas GLY143 has the highest value of residue velocity giving rise to a flat RDF peak for the MP-N3 atom pair. Furthermore, electrostatic and van der Waals interaction energies between N3 and MP-LBD residues are noted to have the negative values. All these parameters explain the binding nature of N3 like inhibitors to the substrate binding sites of COVID-19 main protease. These analysis are expected to be a possible route applicable in drug designing mechanism to restrict the viral replication and transcription of COVID-19.

中文翻译：

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COVID-19主要蛋白酶的结构分析及其与抑制剂N3的相互作用

在这里，我们通过分子动力学模拟分析了COVID-19主蛋白酶（MP）中配体结合域（LBD）的结构特征，然后分析了抑制剂N3和MP-LBD残基之间的相互作用。物理参数的基于时间的变化包括均方根偏差（RMSD），均方根波动（RMSF），回转半径（RG），二面体分布，残留速度，径向分布函数（RDF）和H键表示由重叠的b形桶和柔性a螺旋形成的MP-N3络合物中的折叠态度。在原子对上观察到的尖锐且平坦的RDF峰决定了MP-LBD残基与N3相互作用期间的柔韧性。尽管N3具有更大的溶剂可及性，但它与LBD残基强烈相互作用，导致氢键键合。在LBD残留物中，已发现GLU166的残留速度最低，可为径向距离接近2Å的三个氢键原子对提供清晰的RDF峰，而GLY143的残留速度值最高，从而为MP-N3产生平坦的RDF峰原子对。此外，注意到N 3和MP-LBD残基之间的静电和范德华相互作用能具有负值。所有这些参数说明了N3样抑制剂与COVID-19主蛋白酶的底物结合位点的结合性质。这些分析有望成为可用于限制COVID-19病毒复制和转录的药物设计机制的途径。而GLY143具有最高的残留速度值，从而使MP-N3原子对的RDF峰平坦。此外，注意到N 3和MP-LBD残基之间的静电和范德华相互作用能具有负值。所有这些参数说明了N3样抑制剂与COVID-19主蛋白酶的底物结合位点的结合性质。这些分析有望成为可用于限制COVID-19病毒复制和转录的药物设计机制的途径。而GLY143具有最高的残留速度值，从而使MP-N3原子对的RDF峰平坦。此外，注意到N 3和MP-LBD残基之间的静电和范德华相互作用能具有负值。所有这些参数说明了N3样抑制剂与COVID-19主蛋白酶的底物结合位点的结合性质。这些分析有望成为可用于限制COVID-19病毒复制和转录的药物设计机制的途径。所有这些参数说明了N3样抑制剂与COVID-19主蛋白酶的底物结合位点的结合性质。这些分析有望成为可用于药物设计机制中以限制COVID-19病毒复制和转录的途径。所有这些参数说明了N3样抑制剂与COVID-19主蛋白酶的底物结合位点的结合性质。这些分析有望成为可用于限制COVID-19病毒复制和转录的药物设计机制的途径。