Ganesan Sai J, Matysiak S
Fischell Department of Bioengineering, University of Maryland , College Park, Maryland 20742, United States.
J Chem Theory Comput. 2014 Jun 10;10(6):2569-2576. doi: 10.1021/ct401087a. Epub 2014 May 9.
We present a generic solvated coarse-grained protein model that can be used to characterize the driving forces behind protein folding. Each amino acid is coarse-grained with two beads, a backbone, and a side chain. Although the backbone beads are modeled as polar entities, side chains are hydrophobic, polar, or charged, thus allowing the exploration of how sequence patterning determines a protein fold. The change in orientation of the atoms of the coarse-grained unit is captured by the addition of two oppositely charged dummy particles inside the backbone coarse-grained bead. These two dummy charges represent a dipole that can fluctuate, thus introducing structural polarization into the coarse-grained model. Realistic α/β content is achieved without any biases in the force field toward a particular secondary structure. The dipoles created by the dummy particles interact with each other and drive the protein models to fold into unique structures depending on the amino acid patterning and presence of capping residues. We have also characterized the role of dipole-dipole and dipole-charge interactions in shaping the secondary and supersecondary structure of proteins. Formation of helix bundles and β-strands are also discussed.
我们提出了一种通用的溶剂化粗粒度蛋白质模型，该模型可用于表征蛋白质折叠背后的驱动力。每个氨基酸由两个珠子粗粒度表示，一个主链珠子和一个侧链珠子。虽然主链珠子被建模为极性实体，但侧链是疏水的、极性的或带电荷的，从而能够探索序列模式如何决定蛋白质折叠。通过在主链粗粒度珠子内部添加两个带相反电荷的虚拟粒子来捕捉粗粒度单元原子的方向变化。这两个虚拟电荷代表一个可以波动的偶极子，从而将结构极化引入粗粒度模型。在力场对特定二级结构没有任何偏向的情况下实现了逼真的α/β含量。虚拟粒子产生的偶极子相互作用，并根据氨基酸模式和封端残基的存在驱动蛋白质模型折叠成独特的结构。我们还表征了偶极 - 偶极和偶极 - 电荷相互作用在塑造蛋白质二级和超二级结构中的作用。还讨论了螺旋束和β链的形成。
