Kar Parimal, Gopal Srinivasa Murthy, Cheng Yi-Ming, Predeus Alexander, Feig Michael
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
J Chem Theory Comput. 2013 Aug 13;9(8):3769-3788. doi: 10.1021/ct400230y.
We describe here the PRIMO (PRotein Intermediate Model) force field, a physics-based fully transferable additive coarse-grained potential energy function that is compatible with an all-atom force field for multi-scale simulations. The energy function consists of standard molecular dynamics energy terms plus a hydrogen-bonding potential term and is mainly parameterized based on the CHARMM22/CMAP force field in a bottom-up fashion. The solvent is treated implicitly via the generalized Born model. The bonded interactions are either harmonic or distance-based spline interpolated potentials. These potentials are defined on the basis of all-atom molecular dynamics (MD) simulations of dipeptides with the CHARMM22/CMAP force field. The non-bonded parameters are tuned by matching conformational free energies of diverse set of conformations with that of CHARMM all-atom results. PRIMO is designed to provide a correct description of conformational distribution of the backbone (ϕ/ψ) and side chains (χ) for all amino acids with a CMAP correction term. The CMAP potential in PRIMO is optimized based on the new CHARMM C36 CMAP. The resulting optimized force field has been applied in MD simulations of several proteins of 36-155 amino acids and shown that the root-mean-squared-deviation of the average structure from the corresponding crystallographic structure varies between 1.80 and 4.03 Å. PRIMO is shown to fold several small peptides to their native-like structures from extended conformations. These results suggest the applicability of the PRIMO force field in the study of protein structures in aqueous solution, structure predictions as well as folding of small peptides.
我们在此描述PRIMO（蛋白质中间模型）力场，这是一种基于物理的完全可转移的加性粗粒度势能函数，适用于多尺度模拟的全原子力场。该能量函数由标准分子动力学能量项加上氢键势能项组成，主要基于CHARMM22/CMAP力场以自下而上的方式进行参数化。溶剂通过广义玻恩模型进行隐式处理。键合相互作用要么是简谐的，要么是基于距离的样条插值势。这些势是基于使用CHARMM22/CMAP力场对二肽进行的全原子分子动力学（MD）模拟定义的。非键合参数通过将不同构象集的构象自由能与CHARMM全原子结果的构象自由能相匹配来进行调整。PRIMO旨在通过一个CMAP校正项对所有氨基酸的主链（ϕ/ψ）和侧链（χ）的构象分布进行正确描述。PRIMO中的CMAP势基于新的CHARMM C36 CMAP进行了优化。由此得到的优化力场已应用于对几种含36 - 155个氨基酸的蛋白质的MD模拟，结果表明平均结构相对于相应晶体结构的均方根偏差在1.80至4.03 Å之间变化。结果表明PRIMO能将几种小肽从伸展构象折叠成类似天然的结构。这些结果表明PRIMO力场在研究水溶液中的蛋白质结构、结构预测以及小肽折叠方面具有适用性。
