A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics
A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics
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DOI：
10.1063/5.0019054
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发表时间：
2020-08-14
影响因子：
4.4
通讯作者：
Chong, Lillian T.
中科院分区：
文献类型：
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作者：
Bogetti, Anthony T.;Piston, Hannah E.;Chong, Lillian T.
我们提出了一个新的力场，琥珀ff15 ipq-m，用于模拟蛋白质模拟物在从治疗学到生物材料的应用。该力场是针对典型蛋白质开发的AMBER ff15 ipq力场的扩展，并且能够对通常与混合或“异质”骨架中的天然α残基一起使用的四类人工骨架单元进行建模：手性逆转的D-α-残基，C-α-甲基化的α-残基Aib，带有蛋白质侧链的同源β-残基（β（3）），和两个环状β残基（β（cyc）; APC和ACPC）。ff15 ipq-m力场包括472个唯一的原子电荷和148个唯一的扭转项。与力场的AMBER IPolQ谱系一致，在显式溶剂的存在下使用隐式极化电荷（IPolQ）方案推导出电荷。据我们所知，没有一般的力场报告的日期模型的人工积木的组合在这里检查。此外，我们还推导了计算β（3）Ala和ACPC β残基的骨架酰胺J-偶联常数的Karplus系数。琥珀ff15 ipq-m力场再现实验观察到的J-耦合常数在简单的四肽，并保持预期的构象倾向，在报告的结构的蛋白质/肽含有人工构建块的兴趣-所有的μ s的时间尺度。这些令人鼓舞的结果证明了IPolQ系列力场在模拟天然蛋白质的结构和动力学以及具有蛋白质启发的人工骨架的模拟物的原子细节方面的能力和鲁棒性。
We present a new force field, AMBER ff15ipq-m, for simulations of protein mimetics in applications from therapeutics to biomaterials. This force field is an expansion of the AMBER ff15ipq force field that was developed for canonical proteins and enables the modeling of four classes of artificial backbone units that are commonly used alongside natural alpha residues in blended or "heterogeneous" backbones: chirality-reversed D-alpha-residues, the C-alpha-methylated alpha-residue Aib, homologated beta-residues (beta(3)) bearing proteinogenic side chains, and two cyclic beta residues (beta(cyc); APC and ACPC). The ff15ipq-m force field includes 472 unique atomic charges and 148 unique torsion terms. Consistent with the AMBER IPolQ lineage of force fields, the charges were derived using the Implicitly Polarized Charge (IPolQ) scheme in the presence of explicit solvent. To our knowledge, no general force field reported to date models the combination of artificial building blocks examined here. In addition, we have derived Karplus coefficients for the calculation of backbone amide J-coupling constants for beta(3)Ala and ACPC beta residues. The AMBER ff15ipq-m force field reproduces experimentally observed J-coupling constants in simple tetrapeptides and maintains the expected conformational propensities in reported structures of proteins/peptides containing the artificial building blocks of interest-all on the mu s timescale. These encouraging results demonstrate the power and robustness of the IPolQ lineage of force fields in modeling the structure and dynamics of natural proteins as well as mimetics with protein-inspired artificial backbones in atomic detail.