Prabhavathi Mekala, Sahoo Bijaya Ketan, Bodapati Anna Tanuja Safala, Raju Bethala Samuel
Department of Chemistry, GITAM School of Science, GITAM Deemed to be University, Hyderabad Campus, 502329, India.
Department of Chemistry, Government Degree College for Women, Sangareddy, Telangana, 502001, India.
J Comput Aided Mol Des. 2025 Jun 23;39(1):34. doi: 10.1007/s10822-025-00612-5.
Protein structure and function are an important aspect in cellular organisms. The function of protein depends on its structural integrity. Changes in its structure may affect to its function leading to disease states. Therefore, understanding the structural integrity of protein both in its free and bound states are very important in medicinal chemistry and biophysical aspects of drug-protein interactions. The COVID-19 antiviral drug molnupiravir (MPV) was used for treatment of COVID-19 illness. The effect of MPV on secondary structure of human serum albumin (HSA) has been investigated from a biophysical perceptive using experimental and docking methods based on binding models. Binding strength of MPV with HSA was 10 M order. Observed fluorescence quenching of HSA by MPV was static type with quenching constant of 10 M order. Thermodynamic parameters (ΔG, ∆H, and ∆S) suggested the spontaneity of contact with hydrogen bonding and van der Waals forces are being the primary forces. Binding-induced structural and conformational changes were visible from synchronous fluorescence and circular dichroism (CD) studies. The 3D fluorescence studies further complemented the conformational observations. Molecular docking of MPV with HSA showed its preferred location at site-1 and corroborated the experimental results. 2D diagram and ligplot assisted to analyse the interface residues in docked complex due to binding. The outcome of this study can be useful to decipher the binding behaviour of other drugs and in design of new drugs of better potential besides possible aid in pharmacodynamic studies of similar molecules.
蛋白质结构与功能是细胞生物体中的一个重要方面。蛋白质的功能取决于其结构完整性。其结构的变化可能会影响其功能，导致疾病状态。因此，了解蛋白质在游离态和结合态下的结构完整性在药物 - 蛋白质相互作用的药物化学和生物物理方面都非常重要。新冠抗病毒药物莫努匹拉韦（MPV）被用于治疗新冠疾病。已从生物物理角度，基于结合模型，采用实验和对接方法研究了MPV对人血清白蛋白（HSA）二级结构的影响。MPV与HSA的结合强度为10⁶ M量级。观察到MPV对HSA的荧光猝灭为静态类型，猝灭常数为10⁶ M量级。热力学参数（ΔG、∆H和∆S）表明接触的自发性，氢键和范德华力是主要作用力。从同步荧光和圆二色性（CD）研究中可以看到结合诱导的结构和构象变化。三维荧光研究进一步补充了构象观察结果。MPV与HSA的分子对接显示其在1位点的优先位置，并证实了实验结果。二维图和ligplot有助于分析对接复合物中由于结合而产生的界面残基。这项研究的结果对于解读其他药物的结合行为以及设计更具潜力的新药可能有用，此外还可能有助于类似分子的药效学研究。
