Development of a new physics-based internal coordinate mechanics force field and its application to protein loop modeling.
Development of a new physics-based internal coordinate mechanics force field and its application to protein loop modeling.
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DOI：
10.1002/prot.22896
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发表时间：
2011-02
影响因子：
2.9
通讯作者：
Totrov, Maxim
中科院分区：
文献类型：
--
作者：
Arnautova, Yelena A.;Abagyan, Ruben A.;Totrov, Maxim
我们报告ICMFF的发展，新的力场参数化使用的小分子晶体和量子力学计算的实验数据相结合。ICMFF的主要特点是：（a）将介电常数参数化为凝聚态（ε=2）而不是真空：（B）改进了对氢键相互作用的描述，使用了重原子-氢相互作用的两套货车德瓦耳斯参数;以及（c）改进的骨架共价几何形状和能量，使用新的骨架扭转势和在Cα原子处的键角纳入内部变量集。通过对4-13个残基环的环建模模拟来评估ICMFF的性能。ICMFF与溶剂可及的表面积溶剂化模型相结合，使用大量的环诱饵进行优化。构象采样使用偏置概率蒙特卡罗方法进行。最低能量构象与天然结构的平均/中位骨架均方根偏差为0.25/0.21 μ m（4个残基环）、0.84/0.46 μ m（8个残基环）和1.16/0.73 μ m（12个残基环）。据我们所知，这些结果是显着优于或可比的任何环路建模方法，不考虑晶体包装的日期。此外，我们的方法的准确性与以前报道的最好的结果考虑到晶体环境。我们将这一成功归功于通过细致的参数化实现的新ICM力场的高精度，优化的溶剂模型以及搜索方法的效率。
We report the development of ICMFF, new force field parameterized using a combination of experimental data for crystals of small molecules and quantum mechanics calculations. The main features of ICMFF include: (a) parameterization for the dielectric constant relevant to the condensed state (ε=2) instead of vacuum; (b) an improved description of hydrogen-bond interactions using duplicate sets of van der Waals parameters for heavy atom-hydrogen interactions; and (c) improved backbone covalent geometry and energetics achieved using novel backbone torsional potentials and inclusion of the bond angles at the Cα atoms into the internal variable set. The performance of ICMFF was evaluated through loop modeling simulations for 4-13 residue loops. ICMFF was combined with a solvent-accessible surface area solvation model optimized using a large set of loop decoys. Conformational sampling was carried out using the Biased Probability Monte Carlo method. Average/median backbone root-mean-square deviations of the lowest energy conformations from the native structures were 0.25/0.21 Å for 4 residues loops, 0.84/0.46 Å for 8 residue loops, and 1.16/0.73 Å for 12 residue loops. To our knowledge, these results are significantly better than or comparable to those reported to date for any loop modeling method that does not take crystal packing into account. Moreover, the accuracy of our method is on par with the best previously reported results obtained considering the crystal environment. We attribute this success to the high accuracy of the new ICM force field achieved by meticulous parameterization, to the optimized solvent model, and the efficiency of the search method.
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影响因子：
5.6
作者：
CHOTHIA, C;LESK, AM
通讯作者：
LESK, AM
蛋白质中主链几何形状的构象依赖性。
DOI：
10.1016/j.str.2009.08.012
发表时间：
2009-10-14
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Berkholz DS;Shapovalov MV;Dunbrack RL Jr;Karplus PA
通讯作者：
Karplus PA
影响因子：
--
作者：
BONDI, A
通讯作者：
BONDI, A
影响因子：
2.9
作者：
de Bakker, PIW;DePristo, MA;Blundell, TL
通讯作者：
Blundell, TL
影响因子：
5.6
作者：
ABAGYAN, R;TOTROV, M
通讯作者：
TOTROV, M