NVT模拟时出现水分子空洞，以及NPT时盒子收缩的原理

NVT出现水分子空洞，以及NPT时盒子收缩的原理：

     For a periodic system, constant pressure is the only way to equilibrate density if the starting state is
not correct. For example, the solvent packing scheme used in LEaP can result in a net void when
solvent molecules are subtracted which can aggregate into "vacuum bubbles" in a constant volume
run. Another potential problem are small gaps at the edges of the box. The upshot is that almost every
system needs to be equilibrated at constant pressure (ntb=2, ntp>0) to get to a proper density. But be
sure to equilibrate first (at constant volume) to something close to the final temperature, before turning
on constant pressure.

    NVT时水的聚集导致形成“真空气泡”。

    NPT时，密度平衡会使得盒子的周期性边界收缩

 

所以，在建模时水盒子要加厚：

     越大的体系，一开始水盒子得加的越厚，因为有空隙会收缩，需要保证收缩后仍大于cutoff值+2A，否则一个周期内的蛋白会和另一个周期内的自己作用，而发生形变。。所以水盒子要厚，一般我默认盒子12A起，density也要多步，至少4次5000步，最后看密度波动，波动值小于1%了就可以走下一步了。