Scully J, Hermans J
North Carolina Supercomputing Center, Research Triangle Park.
J Mol Biol. 1994 Jan 14;235(2):682-94. doi: 10.1006/jmbi.1994.1020.
Molecular dynamics simulations have been used to study differences in propensity to form a disulfide-bridged turn conformation by peptides with sequence Ac-Cys-Pro-Xaa-Cys-NMe. The calculations were limited to three peptides, with Xaa = Aib, Gly and Val. The experimental differences in propensity (in terms of free energy differences delta delta G degree) were reproduced within 2 kJ/mol. The use of a reduced 1-4 non-bonded interaction potential was tested in this system, but was found to give slightly worse agreement with experiment. The stability of alternate conformations was determined systematically. Type I and II turn conformations of the Aib compound have similar free energy; the Val compound is most stable in a type I turn conformation (by 8 kJ/mol), while the Gly compound is most stable in a type II turn conformation (by 5 kJ/mol). Different backbone conformations were obtained for the valine compound in simulations in solution and in the crystal. It is concluded that turn conformations with psi i+2 near 0, as typically seen in proteins, are stabilized by intramolecular hydrogen bonding in the confined environment. However, when exposed to solvent, hydrogen bonds with water stabilize conformations with larger or smaller values of psi i+2 that are more similar to free energy minima in the isolated, terminally blocked, residue.
分子动力学模拟已被用于研究具有序列Ac-Cys-Pro-Xaa-Cys-NMe的肽形成二硫键桥连转角构象的倾向差异。计算仅限于三种肽，其中Xaa分别为Aib、Gly和Val。倾向的实验差异（以自由能差ΔΔG°表示）在2 kJ/mol范围内得到了重现。在该系统中测试了简化的1-4非键相互作用势，但发现与实验的一致性略差。系统地确定了交替构象的稳定性。Aib化合物的I型和II型转角构象具有相似的自由能；Val化合物在I型转角构象中最稳定（相差8 kJ/mol），而Gly化合物在II型转角构象中最稳定（相差5 kJ/mol）。在溶液和晶体模拟中，缬氨酸化合物获得了不同的主链构象。得出的结论是，如在蛋白质中常见的，ψi+2接近0的转角构象在受限环境中通过分子内氢键得以稳定。然而，当暴露于溶剂时，与水形成的氢键会稳定ψi+2值更大或更小的构象，这些构象更类似于孤立的、末端封闭的残基中的自由能最小值。
