学习使用GROMACS已经很久了，但是一直停留在很初级的应用上面，对高级技巧并不了解。就连做生物体系几乎必做的MMPBSA分析都没有尝试过。乘着这个假期了解了一下MMPBSA，才知道这个计算方法不仅仅是用于蛋白质-配体体系的结合自由能计算，对于任何一个二聚体都是可以的。另外，Jerkwin老师已经发展出了比之前常用的GMXMMPBSA与g_mmpbsa两种脚本/程序更加简单易用的计算脚本——gmx_mmpbsa。gmx_mmpbsa不但没有GROMACS与APBS程序的版本要求，还可以一步运行获得所有结果，大大降低了MMPBSA的学习成本。
Jerkwin老师的博客中有详尽的使用说明以及与其他两种方法计算结果的比对，另外，gmx_mmpbsa脚本的最新版本也在可以他的github库中找到。
gmx_mmpbsa使用前需安装GRMOMACS与APBS，脚本会自动调用这两个程序进行计算。Ubuntu环境下APBS可以使用sudo apt install apbs直接进行安装。在修改脚本内的变量内容时，如果GROMACS与APBS都已添加进了环境变量，则可简写为：gmx='gmx'以及apbs='apbs'。
脚本运行过程中如果出现某些awk函数未定义的错误，那么还需要安装一下gawk，使用sudo apt install gawk即可。
计算完成后会生成一系列不同结果的文档，这里编写了一个python脚本来进行绘图，顺便复习了一下Pandas与Matplotlib的使用方法。其中有关饼状图的修饰来自于Lemonbit的知乎专栏文章。
# This script is design to plot the mmpbsa calculate results
# from Jerkwin's gmx_mmpbsa script
# Author: Lewisbase
# Date: 2020.02.29
import numpy as np
import pandas as pd
import matplotlib.pyplot as plt
from matplotlib import font_manager as fm
from matplotlib import cm
def readindata(filename):
with open(filename) as f:
text = f.readlines()
index = []
data = np.zeros([len(text)-1,len(text[0].split())-1])
for i in range(1,len(text)):
index.append(text[i].split()[0])
for j in range(1,len(text[i].split())):
if text[i].split()[j] == '|':
data[i-1][j-1] = np.nan
else:
data[i-1][j-1]=float(text[i].split()[j])
columns = text[0].split()[1:]
dataframe = pd.DataFrame(data=data,index=index,columns=columns)
return dataframe
def plot_binding_bar(dataframe):
'''Plot the bar figure from total MMPBSA data'''
names = [('Binding Free Energy\nBinding = MM + PB + SA',
['Binding','MM','PB','SA']),
('Molecule Mechanics\nMM = COU + VDW',
['MM','COU','VDW']),
('Poisson Boltzman\nPB = PBcom - PBpro - PBlig',
['PB','PBcom','PBpro','PBlig']),
('Surface Area\nSA = SAcom - SApro - SAlig',
['SA','SAcom','SApro','SAlig'])]
fig,axs = plt.subplots(2,2,figsize=(8,8),dpi=72)
axs = np.ravel(axs)
for ax,(title,name) in zip(axs,names):
ax.bar(name,dataframe[name].mean(),width=0.5,
yerr=dataframe[name].std(),color='rgby')
for i in range(len(dataframe[name].mean())):
ax.text(name[i],dataframe[name].mean()[i],
'%.3f'%dataframe[name].mean()[i],
ha='center',va='center')
ax.grid(b=True,axis='y')
ax.set_xlabel('Energy Decomposition Term')
ax.set_ylabel('Free energy (kJ/mol)')
ax.set_title(title)
plt.suptitle('MMPBSA Results')
plt.tight_layout()
plt.subplots_adjust(top=0.9)
plt.savefig('MMPBSA_Results.png')
plt.show()
def plot_plot_pie(datas):
'''Plot the composition curve and pie figure'''
fig,axs = plt.subplots(2,2,figsize=(8,8),dpi=72)
axs = np.ravel(axs)
names = [('Composition of MMPBSA',[0,1,4]),
('Composition of MM',[1,2,3]),
('Composition of PBSA',[4,5,6])]
labels = ['res_MMPBSA','resMM','resMM_COU','resMM_VDW',
'resPBSA','resPBSA_PB','resPBSA_SA']
colors = ['black','blue','red']
linestyles = ['-','--',':']
alphas = [1,0.4,0.4]
for ax,(title,name) in zip(axs[:-1],names):
for i in range(len(name)):
ax.plot(range(datas[name[i]].shape[1]),datas[name[i]].mean(),
color=colors[i],alpha=alphas[i],label=labels[name[i]],
linestyle=linestyles[i],linewidth=2.5)
ax.grid(b=True,axis='y')
ax.set_xlabel('Residues No.')
ax.set_ylabel('Free Energy Contribution (kJ/mol)')
ax.legend(loc='best')
ax.set_title(title)
explode = np.zeros([datas[0].shape[1]])
maxposition = np.where(datas[0].mean() == datas[0].mean().abs().max())
maxposition = np.append(maxposition,np.where(datas[0].mean() ==
-1 * datas[0].mean().abs().max()))
explode[maxposition] = 0.4
colors = cm.rainbow(np.arange(datas[0].shape[1])/datas[0].shape[1])
patches, texts, autotexts = axs[-1].pie(datas[0].mean()/datas[0].mean().sum()*100,
explode=explode,labels=datas[0].columns,autopct='%1.1f%%',
colors=colors,shadow=True,startangle=90,labeldistance=1.1,
pctdistance=0.8)
axs[-1].axis('equal') # Equal aspect ratio ensures that pie is drawn as a circle
axs[-1].set_title('Composition of MMPBSA')
# set font size
proptease = fm.FontProperties()
proptease.set_size('xx-small')
# font size include: xx-small,x-small,small,medium,large,x-large.xx-large or numbers
plt.setp(autotexts,fontproperties=proptease)
plt.setp(texts,fontproperties=proptease)
plt.suptitle('MMPBSA Energy Composition')
plt.tight_layout()
plt.subplots_adjust(top=0.9)
plt.savefig('MMPBSA_Energy_Composition.png')
plt.show()
if __name__ == '__main__':
pass
prefix = input('Input the prefix of the calculate results: \n')
files = ['MMPBSA','res_MMPBSA','resMM','resMM_COU','resMM_VDW',
'resPBSA','resPBSA_PB','resPBSA_SA']
datas = []
for file in files:
filename = prefix + '~' + file + '.dat'
datas.append(readindata(filename))
plot_binding_bar(datas[0])
plot_plot_pie(datas[1:])
运行后会将MMPBSA的计算结果汇总为自由能的柱形图，以及各个残基自由能贡献的线状图与饼状图。数据太多时饼状图的标签会堆叠在一起，暂时还没想到很好的处理办法，图像展示如下：
Bar
Plots and Pie
