The PDB format is very old. In an effort to handle its legacy shortcomings, several versions have been made over the years, they are not all readily interchangeable, and not all software can handle each version perfectly. The most important things to watch out for are:
One needs to know well the working system, thus:
The protonation state of the system is critical. Since MD simulations typically don’t allow for bond breaking, the initial protonation of the system must be accurate. Knowing what pH you are trying to reproduce is therefore important to obtain the correct results. If you suspect changing protonation is important to your system and you still want to use classical mechanics, consider simulating both states (protonated and not protonated).
Histidine residues can have three different protonations states even at pH 7, therefore, a correct protonation of this residue is particularly critical. This residue can be protonated at either delta (most common; HSD/HID), epsilon (very common also; HSE/HIE) or at both nitrogens (special situations and low pH; HSP/HIP).
The best way to determine how histidine should be protonated is to look at the the structure. Typically, a histidine residue is protonated if it is close enough to an electron donor (e.g. a glutamic acid), thus creating a hydrogen bond. Since histidines are frequently present at protein active sites, a correct protonation state is particularly important in ligand binding simulations.
In HTMD, one can use
proteinPrepare to help with protonation.
|CT1||0||methylated C-terminus from methyl acetate|
|ACE||0||acetylated N-terminus (to create dipeptide)|
|ACP||0||acetylated N-terminus (for proline dipeptide)|
|ASPP||0||patch for protonated aspartic acid, proton on OD2|
|GLUP||0||patch for protonated glutamic acid, proton on OE2|
|CYSD||-1||patch for deprotonated CYS|
|DISU||+1||patch for disulfides. Patch must be 1-CYS and 2-CYS|
|HS2||+1||patch for neutral His, move proton from ND1 to NE2|
|TP1||-1||patch to convert tyrosine to monoanionic phosphotyrosine|
|TP1A||-1||patch to convert tyrosine to monoanionic phenol-phosphate model compound when generating tyr, use first none last none for terminal patches|
|TP2||-2||patch to convert tyrosine to dianionic phosphotyrosine|
|TP2A||-2||patch to convert tyrosine to dianionic phosphotyrosine when generating tyr, use first none last none for terminal patches this converts a single tyrosine to a phenol phosphate|
|TMP1||-1||patch to convert tyrosine to monoanionic phosphonate ester O -> methylene (see RESI BMPH)|
|TMP2||-2||patch to convert tyrosine to dianionic phosphonate ester O -> methylene (see RESI BMPD)|
|TDF1||-1||patch to convert tyrosine to monoanionic difluoro phosphonate ester O -> methylene (see RESI BDFH)|
|LIG1||0||linkage for cyclic peptide, 1 refers to the C terminus which is a glycine , 2 refers to the N terminus|
|LIG2||0||linkage for cyclic peptide, 1 refers to the C terminus, 2 refers to the N terminus which is a glycine|
|LIG3||0||linkage for cyclic peptide, 1 refers to the C terminus which is a glycine, 2 refers to the N terminus which is a glycine|