Milik M, Skolnick J
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
Proteins. 1993 Jan;15(1):10-25. doi: 10.1002/prot.340150104.
A combination of dynamic Monte Carlo simulation techniques with a hydropathy scale method for the prediction of the location of transmembrane fragments in membrane proteins is described. The new hydropathy scale proposed here is based on experimental data for the interactions of tripeptides with phospholipid membranes (Jacobs, R.E., White, S.H. Biochemistry 26:6127-6134, 1987) and the self-solvation effect in protein systems (Roseman, M.A. J. Mol. Biol. 200:513-522, 1988). The simulations give good predictions both for the state of association and the orientation of the peptide relative to the membrane surface of a number of peptides including Magain2, M2 delta, and melittin. Furthermore, for Pf1 bacteriophage coat protein, in accord with experiment, the simulations predict that the C-terminus forms a transmembrane helix and the N-terminus forms a helix which is adsorbed on the surface of the bilayer. Finally, the present series of simulations provide a number of insights into the mechanism of insertion of peptides into cell membranes.
本文描述了一种将动态蒙特卡罗模拟技术与亲水性标度方法相结合的方法，用于预测膜蛋白中跨膜片段的位置。这里提出的新亲水性标度基于三肽与磷脂膜相互作用的实验数据（雅各布斯，R.E.，怀特，S.H.《生物化学》26:6127 - 6134，1987）以及蛋白质系统中的自溶剂化效应（罗斯曼，M.A.《分子生物学杂志》200:513 - 522，1988）。对于包括马盖宁2、M2δ和蜂毒肽在内的多种肽，模拟对肽与膜表面的缔合状态和取向都给出了良好的预测。此外，对于Pf1噬菌体外壳蛋白，与实验一致，模拟预测C端形成跨膜螺旋，N端形成吸附在双层膜表面的螺旋。最后，本系列模拟为肽插入细胞膜的机制提供了许多见解。
