AB-INITIO STRUCTURE PREDICTION FOR SMALL POLYPEPTIDES AND PROTEIN-FRAGMENTS USING GENETIC ALGORITHMS
AB-INITIO STRUCTURE PREDICTION FOR SMALL POLYPEPTIDES AND PROTEIN-FRAGMENTS USING GENETIC ALGORITHMS
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DOI：
10.1002/prot.340230319
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发表时间：
1995-11-01
期刊：
影响因子：
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通讯作者：
MOULT, J
中科院分区：
文献类型：
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作者：
PEDERSEN, JT;MOULT, J
从头算折叠模拟已经在三个肽上进行，使用基于遗传算法的搜索方法，该方法在全原子表示上运行。用实验结构的平均力分析势参数化的经验力场来评价构象。力场中的主导项是局域和非局域主链静电和疏水效应。其中两个模拟的结构是完整蛋白质的片段（嗜酸性粒细胞衍生的神经毒素（EDN）和枯草菌素前肽），它们被确定为可能是折叠的起始位点。其中一种（EDN）的实验结构随后被发现与该预测一致（使用局部疏水埋藏作为独立折叠的决定因素）。对这两种多肽结构的模拟只取得了部分成功。最成功的折叠模拟是与凝血因子VIII的膜结合域（Membind）对应的22个残基肽。对该肽进行了三次模拟，发现其最低能构象与实验结构最相似，其构象的c - α均方根偏差为4.4埃。虽然这些模拟部分成功，但仍有许多未解决的问题，我们希望能够在下一次结构预测实验中解决这些问题。(C) 1995 Wiley-Liss, Inc。
Ab initio folding simulations have been performed on three peptides, using a genetic algorithm-based search method which operates on a full atom representation. Conformations are evaluated with an empirical force field parameterized by a potential of mean force analysis of experimental structures. The dominant terms in the force field are local and nonlocal main chain electrostatics and the hydrophobic effect. Two of the simulated structures were for fragments of complete proteins (eosinophil-derived neurotoxin (EDN) and the subtilisin propeptide) that were identified as being likely initiation sites for folding. The experimental structure of one of these (EDN) was subsequently found to be consistent with that prediction (using local hydrophobic burial as the determinant for independent folding). The simulations of the structures of these two peptides were only partly successful. The most successful folding simulation was that of a 22-residue peptide corresponding to the membrane binding domain of blood coagulation factor VIII (Membind). Three simulations were performed on this peptide and the lowest energy conformation was found to be the most similar to the experimental structure, The conformation of this peptide was determined with a C-alpha rms deviation of 4.4 Angstrom. Although these simulations were partly successful there are still many unresolved problems, which we expect to be able to address in the next structure prediction experiment. (C) 1995 Wiley-Liss, Inc.