Gromacs模拟计算：从建模到自由能的完整经验指南

PDB结构 → pdb2gmx(拓扑) → 盒子 → 溶剂化 → 加离子
→ EM(能量最小化) → NVT平衡 → NPT平衡 → 生产MD → 分析

# em.mdp
integrator           = steep
emtol                = 1000.0    # kJ/mol/nm
emstep               = 0.01      # nm
nsteps               = 50000
cutoff-scheme        = Verlet
coulombtype          = PME
rcoulomb             = 1.0       # nm
rvdw                 = 1.0       # nm
DispCorr             = EnerPres  # 色散校正

# nvt.mdp
integrator           = md
dt                   = 0.002     # 2 fs
nsteps               = 250000    # 500 ps
continuation         = no
constraint_algorithm = lincs
constraints          = h-bonds
cutoff-scheme        = Verlet
coulombtype          = PME
tcoupl               = V-rescale
tc-grps              = Protein Non-Protein
tau_t                = 0.1 0.1
ref_t                = 300 300
pcoupl               = no
define               = -DPOSRES   # 位置约束

# npt.mdp (与NVT相同，增加压力耦合)
pcoupl               = Parrinello-Rahman
pcoupltype           = isotropic
tau_p                = 2.0
ref_p                = 1.0
compressibility      = 4.5e-5
# 移除位置约束: 删除 define = -DPOSRES

# md.mdp
integrator           = md
dt                   = 0.002
nsteps               = 25000000   # 50 ns
tcoupl               = V-rescale
tc-grps              = Protein Non-Protein
tau_t                = 0.1 0.1
ref_t                = 300 300
pcoupl               = Parrinello-Rahman
pcoupltype           = isotropic
tau_p                = 2.0
ref_p                = 1.0
constraints          = h-bonds
nstxout-compressed   = 5000      # 每10ps保存轨迹
nstenergy            = 5000
nstlog               = 5000

# RMSD (相对于参考结构)
echo "Backbone" | gmx rms -s md.tpr -f md.xtc -o rmsd_backbone.xvg -tu ns

# RMSF (残基灵活性)
echo "C-alpha" | gmx rmsf -s md.tpr -f md.xtc -o rmsf.xvg -res

# 回转半径
echo "Protein" | gmx gyrate -s md.tpr -f md.xtc -o gyrate.xvg

# 二级结构
echo "Protein" | gmx dssp -s md.tpr -f md.xtc -o ss.xpm

# 氢键分析
echo "Protein" "Drug" | gmx hbond -s md.tpr -f md.xtc -num hbond.xvg

# 距离监控
echo "Protein" "Drug" | gmx distance -s md.tpr -f md.xtc -select 'com of group 1 plus com of group 2' -o distance.xvg

# 接触面积
echo "Protein" "Drug" | gmx sasa -s md.tpr -f md.xtc -o sasa.xvg -surface Protein -output group

# 提取PC1和PC2
gmx covar -s md.tpr -f md.xtc -o eigenvalues.xvg -v eigenvectors.trr
gmx anaeig -v eigenvectors.trr -s md.tpr -f md.xtc -proj pc1pc2.xvg -first 1 -last 2

# 用sham生成自由能面
gmx sham -f pc1pc2.xvg -notime -bin 100 -land -ls FES.xpm

# 安装g_mmpbsa
# 提取100帧轨迹
gmx trjconv -f md.xtc -s md.tpr -o frames.xtc -fit rot+trans -dt 100

# 计算
g_mmpbsa -f frames.xtc -s md.tpr -i mmpbsa.mdp -mm out_mm.dat -pol out_pol.dat

# 自由能微扰(FEP)
gmx grompp -f fep_A.mdp -c complex.gro -p topol_A.top -o fep_A.tpr
gmx mdrun -deffnm fep_A -dhdl

# BAR分析
gmx bar -f fep_A.xvg -o bar.xvg

# 1. 拉伸产生初始构型
gmx grompp -f pull.mdp -c npt.gro -p topol.top -o pull.tpr
gmx mdrun -deffnm pull -pf pullf.xvg

# 2. 生成伞形采样窗口
gmx wham -s pull.tpr -f pull_*.xvg -o pmf.xvg

# 自动使用GPU
gmx mdrun -deffnm md -nb gpu

# 指定GPU ID
gmx mdrun -deffnm md -gpu_id 01

# 多节点并行
gmx mdrun -deffnm md -ntmpi 4 -ntomp 8 -npme 1