Assembly of protein structure from sparse experimental data: An efficient Monte Carlo model
Assembly of protein structure from sparse experimental data: An efficient Monte Carlo model
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DOI：
10.1002/(sici)1097-0134(19980901)32:4
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发表时间：
1998-09-01
期刊：
影响因子：
--
通讯作者：
Skolnick, J
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文献类型：
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作者：
Kolinski, A;Skolnick, J
提出了一种新的高效的方法，从已知的，松散编码的二级结构的限制和稀疏信息的精确侧链接触蛋白质三级结构的组装和评估。该方法是基于一种新的非常简单的方法，用于蛋白质结构和动力学的简化建模，其中蛋白质被描述为连接侧链质量中心的晶格链，而不是气体。该模型具有隐式的内置多体相关性，模拟短期和长期的包装偏好，氢键协同性和描述疏水相互作用的平均力势，由于简单的蛋白质表示和模型力场的定义，蒙特卡罗算法是至少一个数量级的速度比以前公布的蒙特卡罗算法的结构组装。与现有算法相比，新方法需要较少数量的三级限制来成功折叠组装;平均而言，与每四个残基一个三级限制相比，每七个残基一个三级限制。例如，对于较小的蛋白质，如蛋白质G的B结构域，所得结构具有坐标均方根偏差（cRMSD），其与实验结构相差约3埃;对于肌红蛋白，产生骨架CRMSD为4.3埃的结构，对于247个残基的TIM桶，所得折叠的CRMSD为约6埃。正如所预期的，增加三级约束的数量提高了组装结构的精度。新方法的可靠性和鲁棒性应使其常规应用程序的模型建立协议的基础上，各种（非常稀疏）实验得出的结构约束。(C)1998 Wiley-Liss，Inc.
A new efficient method for the assembly of protein tertiary structure from known, loosely encoded secondary structure restraints and sparse information about exact side chain contacts is proposed and evaluated. The method is based on a new very simple method for the reduced modeling of protein structure and dynamics, where the protein is described as a lattice chain connecting side chain centers of mass rather than Gas. The model has implicit built-in multibody correlations that simulate short- and long-range packing preferences, hydrogen bonding cooperativity and a mean force potential describing hydrophobic interactions, Due to the simplicity of the protein representation and definition of the model force field, the Monte Carlo algorithm is at least an order of magnitude faster than previously published Monte Carlo algorithms for structure assembly. In contrast to existing algorithms, the new method requires a smaller number of tertiary restraints for successful fold assembly; on average, one for every seven residues as compared to one for every four residues, For example, for smaller proteins such as the B domain of protein G;, the resulting structures have a coordinate root mean square deviation (cRMSD), which is about 3 Angstrom from the experimental structure; for myoglobin, structures whose backbone cRMSD is 4.3 Angstrom are produced, and for a 247-residue TIM barrel, the cRMSD of the resulting folds is about 6 Angstrom. As would be expected, increasing the number of tertiary restraints improves the accuracy of the assembled structures. The reliability and robustness of the new method should enable its routine application in model building protocols based on various (very sparse) experimentally derived structural restraints. (C) 1998 Wiley-Liss, Inc.