Russian State Medical University, ul. Ostrovityanova 1, 117997 Moscow, Russia.
Biochemistry (Mosc). 2011 Dec;76(12):1321-36. doi: 10.1134/S0006297911120054.
Conformational and dynamic properties of proteins and peptides play an important role in their functioning. However, mechanisms that underlie this influence have not been fully elucidated. In the present work we computationally constructed analogs of heptapeptide AFP(14-20) (LDSYQCT) - one of the biologically active sites of human α-fetoprotein (AFP) - to study their conformational and dynamic properties using molecular dynamics simulation. Analogs were obtained by point substitutions of amino acid residues taking into account differences in their physicochemical properties and also on the basis of analysis of amino acid substitutions in the AFP(14-20)-like motifs revealed in different physiologically active proteins. It is shown that changes in conformational mobility of amino acid residues of analogs are due to disruption or arising of intramolecular interactions that, in turn, determine existence of steric restrictions during rotation around covalent bonds of the peptide backbone. Substitution of an amino acid by another one with significant difference in physicochemical properties may not lead to remarkable changes in conformational and dynamic properties of the peptide if intramolecular interactions remain unchanged.
蛋白质和肽的构象和动态特性在它们的功能中起着重要作用。然而，这种影响的机制尚未完全阐明。在本工作中，我们通过计算构建了人α-胎蛋白（AFP）中具有生物活性的七肽 AFP(14-20)（LDSYQCT）的类似物，以使用分子动力学模拟研究它们的构象和动态特性。类似物是通过考虑氨基酸残基的物理化学性质的差异以及基于对在不同生理活性蛋白中发现的 AFP(14-20) 样基序中的氨基酸取代的分析，进行点取代获得的。结果表明，类似物中氨基酸残基构象迁移率的变化是由于破坏或形成分子内相互作用所致，而这些相互作用又决定了肽主链中键旋转时的空间位阻的存在。如果分子内相互作用保持不变，那么用物理化学性质有显著差异的另一种氨基酸取代氨基酸可能不会导致肽的构象和动态性质发生显著变化。
