Yarov-Yarovoy Vladimir, Schonbrun Jack, Baker David
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
Proteins. 2006 Mar 1;62(4):1010-25. doi: 10.1002/prot.20817.
We describe the adaptation of the Rosetta de novo structure prediction method for prediction of helical transmembrane protein structures. The membrane environment is modeled by embedding the protein chain into a model membrane represented by parallel planes defining hydrophobic, interface, and polar membrane layers for each energy evaluation. The optimal embedding is determined by maximizing the exposure of surface hydrophobic residues within the membrane and minimizing hydrophobic exposure outside of the membrane. Protein conformations are built up using the Rosetta fragment assembly method and evaluated using a new membrane-specific version of the Rosetta low-resolution energy function in which residue-residue and residue-environment interactions are functions of the membrane layer in addition to amino acid identity, distance, and density. We find that lower energy and more native-like structures are achieved by sequential addition of helices to a growing chain, which may mimic some aspects of helical protein biogenesis after translocation, rather than folding the whole chain simultaneously as in the Rosetta soluble protein prediction method. In tests on 12 membrane proteins for which the structure is known, between 51 and 145 residues were predicted with root-mean-square deviation <4 A from the native structure.
我们描述了将Rosetta从头结构预测方法应用于螺旋跨膜蛋白结构预测的适应性调整。通过将蛋白质链嵌入到一个由平行平面表示的模型膜中来模拟膜环境,这些平行平面为每次能量评估定义了疏水、界面和极性膜层。通过最大化膜内表面疏水残基的暴露程度并最小化膜外疏水暴露来确定最佳嵌入方式。使用Rosetta片段组装方法构建蛋白质构象,并使用Rosetta低分辨率能量函数的新膜特异性版本进行评估,其中除了氨基酸同一性、距离和密度外,残基-残基和残基-环境相互作用还是膜层的函数。我们发现,通过将螺旋依次添加到不断增长的链中可以获得能量更低且更类似天然的结构,这可能模拟了转运后螺旋蛋白生物合成的某些方面,而不是像Rosetta可溶性蛋白预测方法那样同时折叠整个链。在对12种已知结构的膜蛋白进行的测试中,预测的51至145个残基与天然结构的均方根偏差<4 Å。