A protein evolution model with independent sites that reproduces site-specific amino acid distributions from the Protein Data Bank.
A protein evolution model with independent sites that reproduces site-specific amino acid distributions from the Protein Data Bank.
复制标题
DOI：
10.1186/1471-2148-6-43
复制
发表时间：
2006-05-31
影响因子：
3.4
通讯作者：
Vendruscolo M
中科院分区：
文献类型：
--
作者：
Bastolla U;Porto M;Roman HE;Vendruscolo M
由于热力学稳定性是蛋白质的一种全局性质，在进化过程中必须保持，所以蛋白质序列中给定位置的选择压力取决于其他位置上存在的氨基酸。然而，如果明确考虑位点之间的这种相关性，旨在重建大分子进化历史的分子进化模型在计算上就会变得难以处理。
我们引入了一种进化模型，其中位点在结构稳定性守恒的全局约束下独立进化。该模型包括一个选择过程，它取决于两个疏水性参数，这两个参数可以从蛋白质序列中计算得出，无需任何拟合，以及一个突变过程，我们考虑了多种突变模型。它定量地重现了蛋白质进化的结构约束中性（SCN）模拟结果，在该模拟中，天然态的稳定性被明确计算并保持。然后，我们将预测的位点特异性氨基酸分布与从蛋白质数据库（PDB）中采样得到的分布进行比较。突变模型的参数数量在0到5之间变化，通过数据进行拟合。对于一个没有自由参数且不考虑遗传密码的突变模型，预测的和观察到的位点特异性氨基酸分布之间的平均相关系数大于<r>=0.70。相比之下，只考虑没有选择的突变过程，在有三个拟合参数的情况下，平均相关系数为<r>=0.56。最适合数据的突变模型考虑了CpG二核苷酸处突变率的增加，在有五个参数的情况下，得到<r>=0.90。
我们提出的有效选择过程很好地重现了蛋白质数据库（PDB）中蛋白质序列所观察到的氨基酸分布。它的简单性使其在系统发育研究的似然计算中非常有前景。有趣的是，在这种方法中，突变过程影响有效选择过程，即选择和突变必须相互交织，才能获得有效独立的位点。突变和选择之间的这种相互依存关系反映了突变对进化过程的深刻影响：突变的偏向影响进化中蛋白质的热力学性质，这与细菌蛋白质组的比较研究一致，它还影响可接受突变的速率。
Since thermodynamic stability is a global property of proteins that has to be conserved during evolution, the selective pressure at a given site of a protein sequence depends on the amino acids present at other sites. However, models of molecular evolution that aim at reconstructing the evolutionary history of macromolecules become computationally intractable if such correlations between sites are explicitly taken into account. We introduce an evolutionary model with sites evolving independently under a global constraint on the conservation of structural stability. This model consists of a selection process, which depends on two hydrophobicity parameters that can be computed from protein sequences without any fit, and a mutation process for which we consider various models. It reproduces quantitatively the results of Structurally Constrained Neutral (SCN) simulations of protein evolution in which the stability of the native state is explicitly computed and conserved. We then compare the predicted site-specific amino acid distributions with those sampled from the Protein Data Bank (PDB). The parameters of the mutation model, whose number varies between zero and five, are fitted from the data. The mean correlation coefficient between predicted and observed site-specific amino acid distributions is larger than <r> = 0.70 for a mutation model with no free parameters and no genetic code. In contrast, considering only the mutation process with no selection yields a mean correlation coefficient of <r> = 0.56 with three fitted parameters. The mutation model that best fits the data takes into account increased mutation rate at CpG dinucleotides, yielding <r> = 0.90 with five parameters. The effective selection process that we propose reproduces well amino acid distributions as observed in the protein sequences in the PDB. Its simplicity makes it very promising for likelihood calculations in phylogenetic studies. Interestingly, in this approach the mutation process influences the effective selection process, i.e. selection and mutation must be entangled in order to obtain effectively independent sites. This interdependence between mutation and selection reflects the deep influence that mutation has on the evolutionary process: The bias in the mutation influences the thermodynamic properties of the evolving proteins, in agreement with comparative studies of bacterial proteomes, and it also influences the rate of accepted mutations.
登录
查看更多内容
DOI：
10.1073/pnas.96.19.10689
发表时间：
1999-09-14
影响因子：
11.1
作者：
Bornberg-Bauer, E;Chan, HS
通讯作者：
Chan, HS
影响因子：
3.9
作者：
BERNARDI, G;BERNARDI, G
通讯作者：
BERNARDI, G
影响因子：
2
作者：
Bastolla, U;Roman, HE;Vendruscolo, M
通讯作者：
Vendruscolo, M
影响因子：
5.6
作者：
CASARI, G;SIPPL, MJ
通讯作者：
SIPPL, MJ
DOI：
10.1016/s0378-4371(02)01079-8
发表时间：
2002-11-01
影响因子：
3.3
作者：
Dokholyan, NV;Mirny, LA;Shakhnovich, EI
通讯作者：
Shakhnovich, EI