Finkelstein Alexei V
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
Chem Cent J. 2007 Jul 30;1:21. doi: 10.1186/1752-153X-1-21.
The prediction of ligand binding or protein structure requires very accurate force field potentials - even small errors in force field potentials can make a 'wrong' structure (from the billions possible) more stable than the single, 'correct' one. However, despite huge efforts to optimize them, currently-used all-atom force fields are still not able, in a vast majority of cases, even to keep a protein molecule in its native conformation in the course of molecular dynamics simulations or to bring an approximate, homology-based model of protein structure closer to its native conformation.
A strict analysis shows that a specific coupling of multi-atom Van der Waals interactions with covalent bonding can, in extreme cases, increase (or decrease) the interaction energy by about 20-40% at certain angles between the direction of interaction and the covalent bond. It is also shown that on average multi-body effects decrease the total Van der Waals energy in proportion to the square root of the electronic component of dielectric permittivity corresponding to dipole-dipole interactions at small distances, where Van der Waals interactions take place.
The study shows that currently-ignored multi-atom Van der Waals interactions can, in certain instances, lead to significant energy effects, comparable to those caused by the replacement of atoms (for instance, C by N) in conventional pairwise Van der Waals interactions.
预测配体结合或蛋白质结构需要非常精确的力场势——即使力场势中存在微小误差，也可能使“错误”的结构（从数十亿种可能的结构中）比单一的“正确”结构更稳定。然而，尽管人们付出了巨大努力来优化它们，但在绝大多数情况下，目前使用的全原子力场甚至无法在分子动力学模拟过程中使蛋白质分子保持其天然构象，也无法使基于同源性的蛋白质结构近似模型更接近其天然构象。
严格分析表明，在相互作用方向与共价键之间的特定角度下，多原子范德华相互作用与共价键的特定耦合在极端情况下可使相互作用能增加（或减少）约20% - 40%。研究还表明，平均而言，多体效应会使总范德华能与在发生范德华相互作用的小距离处对应偶极 - 偶极相互作用的介电常数电子分量的平方根成比例降低。
该研究表明，目前被忽视的多原子范德华相互作用在某些情况下可能导致显著的能量效应，这与传统成对范德华相互作用中原子取代（例如，用N取代C）所引起的能量效应相当。
