Department of Chemistry, New York University, New York, New York 10003, USA.
J Phys Chem B. 2010 Dec 9;114(48):15935-40. doi: 10.1021/jp109865y. Epub 2010 Nov 15.
When only equilibrium thermodynamics or averages of position-dependent functions in classical molecular dynamics calculations are sought, the choice of the atomic masses in the Hamiltonian becomes irrelevant. Consequently, the masses can be used as free parameters to help improve conformational sampling efficiency in the spirit of Bennett's mass-tensor dynamics (Bennett, C. H. J. Comput. Phys. 1975, 19, 267.). Here we report on the effect of reducing side-chain and solvent masses on the folding behavior of a 9-residue hairpin-forming peptide in solution. A physical motivation for reducing the solvent mass is an effective reduction in solvent viscosity. Side-chain mass scaling is motivated by the idea of solvent potentials of mean force which are employed in select coarse-grained protein models. In the limit of very large mass differences, the mass reduction effectively creates an adiabatic decoupling between solvent, side-chain, and backbone motions, so that both the backbone and side chains move on the instantaneous solvent potential of mean force (PMF) surface, and the backbone additionally moves on the side-chain PMF. Because of the arbitrariness in the choice of masses, this limit only needs to be reached approximately in practice. In particular, we show that a 10-fold reduction in solvent masses and a side-chain mass scale that is intermediate between the scaled solvent and the backbone lead to a quantitative enhancement in conformational sampling.
当仅寻求平衡热力学或经典分子动力学计算中位置相关函数的平均值时，哈密顿中的原子质量的选择变得无关紧要。因此，可以将质量用作自由参数，以帮助提高构象采样效率，这符合 Bennett 的质量张量动力学（Bennett，C.H.J. Comput. Phys. 1975，19，267.）的精神。在这里，我们报告了在溶液中减少侧链和溶剂质量对 9 残基发夹形成肽折叠行为的影响。减少溶剂质量的物理动机是有效降低溶剂粘度。侧链质量缩放的动机是溶剂平均力势的概念，该概念用于选择粗粒化蛋白质模型。在质量差异非常大的极限下，质量减少有效地在溶剂、侧链和骨架运动之间创建了绝热解耦，使得骨架和侧链都在瞬时溶剂平均力势（PMF）表面上移动，并且骨架另外在侧链 PMF 上移动。由于质量选择的任意性，实际上只需要接近该极限。特别是，我们表明，溶剂质量降低 10 倍，以及介于缩放溶剂和骨架之间的侧链质量缩放比例，可以定量提高构象采样效率。
