3.20 阳性化合物MD

蛋白准备（晶体结构）

85.23 /home/databank_70t/zzy/project/hsbd/active_control/sys-pre/pro/pdb2pqr
pdb2pqr30  ../7cmd.pdb 7cmd.pqr  --ff AMBER --ffout AMBER --with-ph 7.4 --pdb-output 7cmd_complex.pdb
grep -v HETATM 7cmd_complex.pdb |awk '$5=="A"{print}' >7cmd_apo_clean.pdb


pdb2pqr30  ../7vh8.pdb 7vh8.pqr  --ff AMBER --ffout AMBER --with-ph 7.4 --pdb-output 7vh8_complex.pdb
grep -v HETATM 7vh8_complex.pdb >7vh8_apo_clean.pdb

配体准备

坐标信息（PDB)

质子化预测

23 /home/databank_70t/zzy/project/hsbd/active_control/sys-pre/ligand/ligprep
for a in `cat index`;do ~/software/Schrodinger_Suites_2021-2/ligprep -R e -epik -ph 7.4 -pht 0.0 -isd ../${a}.sdf -osd ./${a}.sdf;done


mv 7vh8_B_4WI.sdf nirmatrelvir.sdf
mv 7cmd_E_TTT.sdf GRL0617.sdf

高斯优化

23 /home/databank_70t/zzy/project/hsbd/2025-4bioactive/sys-pre/ligand/g16
# 使用antechamber生成配体小分子参数（85.23）
for i in `cat index`;do mkdir $i;cd $i;antechamber -i ../../ligprep/${i}.sdf -fi sdf -o $i.gjf -fo gcrt;sed -i '1,3d' $i.gjf;sed -i '1i %mem=4GB\n%nproc=4\n#B3LYP/6-31G* Pop=MK iop(6/33=2) iop(6/42=6) opt' $i.gjf;cd ../;done


# 提交 高斯优化任务 10:33
23 /home/databank_70t/zzy/project/hsbd/2025-4bioactive/sys-pre/ligand/g16
for i in `cat index`;do cd $i;antechamber -i $i.log -fi gout -o $i.prep -fo prepi -c resp;parmchk2 -i $i.prep -f prepi -o $i.frcmod -a y;cd ../;done

复合物体系准备

23 /home/databank_70t/zzy/project/hsbd/active_control/sys-pre/ligand/atom_name_check
cp ../g16/index ./
sh do.sh
# 可视化检查

tleap

# 23 /home/databank_70t/zzy/project/hsbd/active_control/sys-pre/tleap
# 加载环境
source ~/zzy/ff19sb.sh
for i in `cat index`;do mkdir -p $i;done


cp ../ligand/g16/GRL0617/*frcmod ./pl-monomer-7cmd/lig.frcmod
cp ../ligand/g16/GRL0617/*prep ./pl-monomer-7cmd/lig.prep
cp ../ligand/atom_name_check/GRL0617/LIG.PDB ./pl-monomer-7cmd/lig.pdb
cp ../pro/pdb2pqr/7cmd_apo_clean.pdb ./pl-monomer-7cmd/pro.pdb


cp ../ligand/g16/nirmatrelvir/*frcmod ./3cl-monomer-7vh8/lig.frcmod
cp ../ligand/g16/nirmatrelvir/*prep ./3cl-monomer-7vh8/lig.prep
cp ../ligand/atom_name_check/nirmatrelvir/LIG.PDB ./3cl-monomer-7vh8/lig.pdb
cp ../pro/pdb2pqr/7vh8_apo_clean.pdb ./3cl-monomer-7vh8/pro.pdb


for  i in `cat index`;do cp md_parm_gen_chinese.py $i;cd $i;python md_parm_gen_chinese.py 1;cd ../;done


# 可视化检查

amber_to_gmx

# 23 /home/databank_70t/zzy/project/hsbd/active_control/sys-pre/amber_to_gmx
####################################  do.sh  #############################################
for i in `cat index`
do 
mkdir -p $i
cp ../tleap/$i/complex* $i
cd $i
cp ../amber_to_gmx-add_restraint.py ./
python amber_to_gmx-add_restraint.py 0 complex.prmtop complex.inpcrd
python amber_to_gmx-add_restraint.py 1
(echo '1|13'; echo 'q') | gmx_mpi make_ndx -f gmx.gro -o index.ndx
echo 1|gmx_mpi genrestr -f gmx.gro -n index.ndx -o posre1.itp
cd ../
done
############################################################################################


#  根据配体原子数生成 posre2.itp (原子数+4=行数）
sed -n '1,47p' pl-monomer-7cmd/posre1.itp > pl-monomer-7cmd/posre2.itp 
sed -n '1,73p' 3cl-monomer-7vh8/posre1.itp > 3cl-monomer-7vh8/posre2.itp

预平衡

# 8-4090（75.3） /home/dddc/zyzhou/project/hsbd
scp -r dddc@172.21.85.23:/home/databank_70t/zzy/project/hsbd/active_control ./


# min-nvt-npt.sh 在mdp文件合适的情况下仅需要修改工作路径，就可以自动完成所有体系的预平衡


dddc@gpu-4090:/home/data/zzy/project/hsbd/2025-4bioactive/pre-equ$ nohup bash min-nvt-npt.sh &
[1] 2697051

MD模拟任务

3cl-monomer-7vh8

75.3 /home/dddc/zyzhou/project/hsbd/active_control/cmd/100ns/1486-70-0-dock-PL

pl-monomer-7cmd 

75.3 /home/dddc/zyzhou/project/hsbd/active_control/cmd/100ns/56083-03-5-dock-3CL