Application of the frozen atom approximation to the GB/SA continuum model for solvation free energy
Application of the frozen atom approximation to the GB/SA continuum model for solvation free energy
复制标题
冻结原子近似在溶剂化自由能 GB/SA 连续介质模型中的应用
DOI：
10.1002/jcc.1167
复制
发表时间：
2002
影响因子：
3
通讯作者：
W. Still
中科院分区：
文献类型：
--
作者：
Olgun Guvench;J. Weiser;P. Shenkin;I. Kolossváry;W. Still
广义玻恩/表面积（GB/SA）连续模型溶剂化自由能是一个快速和准确的替代使用离散水分子的溶剂化体系的分子模拟。然而，大溶剂化的分子系统，如酶-配体复合物的计算研究仍然可以计算昂贵，即使连续溶剂化方法，仅仅是因为大量的原子在溶质分子。因为在这样的系统中，通常只有系统的相对小的部分，如配体结合位点正在研究中，所以计算系统中所有原子的能量和导数变得不那么有吸引力。为了减少计算，同时保持高能量精度，远离感兴趣的原子经常被冻结;也就是说，它们的坐标不变。这种冻结的原子在模拟过程中不需要能量和衍生更新。在这里，我们描述的方法和结果适用于冻结原子的方法，广义玻恩（GB）和溶剂可及表面积（SASA）的GB/SA连续模型的部分溶剂化自由能。对于严格成对的能量项，例如库仑和货车-der-Waals能量，来自冻结原子对的贡献可以忽略。这使得能量差异不受构象的影响，构象只在非冻结原子的位置变化。然而，由于GB分析形式的非局部性质，从GB计算中排除此类对会导致不可接受的不准确性。为了将冻结原子方案应用于GB计算，冻结原子区域内的缓冲区是根据用户可定义的非冻结原子截止距离生成的。在GB计算中保留了缓冲区中冻结原子之间的某些成对相互作用。这使得高精度的构象GB比较，以保持同时实现显着节省计算时间相比，完整的（非冻结）计算。一个类似的方法，使用一个缓冲区的冻结原子采取的SASA计算。SASA计算本质上是局部的，因此保持了精确的SASA能量。对于冷冻原子的情况，在缓冲区为8 μ m的情况下，相对于非冷冻的情况，细胞色素P450与结合的樟脑配体的三种不同构象的能量差异具有极好的一致性。对于各种最小化协议，模拟运行速度快2至10.5倍，内存使用减少了1.5至5倍。因此，应用冷冻原子方法进行GB/SA计算可以使计算易于处理的生物学和医学上重要的模拟，如用于研究溶剂化环境中的配体-受体结合构象和能量的模拟。© 2002 Wiley Periodicals，Inc. J Comput Chem 23：214-221，2002
The generalized Born/surface area (GB/SA) continuum model for solvation free energy is a fast and accurate alternative to using discrete water molecules in molecular simulations of solvated systems. However, computational studies of large solvated molecular systems such as enzyme–ligand complexes can still be computationally expensive even with continuum solvation methods simply because of the large number of atoms in the solute molecules. Because in such systems often only a relatively small portion of the system such as the ligand binding site is under study, it becomes less attractive to calculate energies and derivatives for all atoms in the system. To curtail computation while still maintaining high energetic accuracy, atoms distant from the site of interest are often frozen; that is, their coordinates are made invariant. Such frozen atoms do not require energetic and derivative updates during the course of a simulation. Herein we describe methodology and results for applying the frozen atom approach to both the generalized Born (GB) and the solvent accessible surface area (SASA) parts of the GB/SA continuum model for solvation free energy. For strictly pairwise energetic terms, such as the Coulombic and van‐der‐Waals energies, contributions from pairs of frozen atoms can be ignored. This leaves energetic differences unaffected for conformations that vary only in the positions of nonfrozen atoms. Due to the nonlocal nature of the GB analytical form, however, excluding such pairs from a GB calculation leads to unacceptable inaccuracies. To apply a frozen‐atom scheme to GB calculations, a buffer region within the frozen‐atom zone is generated based on a user‐definable cutoff distance from the nonfrozen atoms. Certain pairwise interactions between frozen atoms in the buffer region are retained in the GB computation. This allows high accuracy in conformational GB comparisons to be maintained while achieving significant savings in computational time compared to the full (nonfrozen) calculation. A similar approach for using a buffer region of frozen atoms is taken for the SASA calculation. The SASA calculation is local in nature, and thus exact SASA energies are maintained. With a buffer region of 8 Å for the frozen‐atom cases, excellent agreement in differences in energies for three different conformations of cytochrome P450 with a bound camphor ligand are obtained with respect to the nonfrozen cases. For various minimization protocols, simulations run 2 to 10.5 times faster and memory usage is reduced by a factor of 1.5 to 5. Application of the frozen atom method for GB/SA calculations thus can render computationally tractable biologically and medically important simulations such as those used to study ligand–receptor binding conformations and energies in a solvated environment. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 214–221, 2002
影响因子：
56.9
作者：
Duan, Y;Kollman, PA
通讯作者：
Kollman, PA
DOI：
10.1073/pnas.84.10.3086
发表时间：
1987-05-01
影响因子：
11.1
作者：
OOI, T;OOBATAKE, M;SCHERAGA, HA
通讯作者：
SCHERAGA, HA