Appendix A. Nonbonded Parameters for OPTIMOL/MMFF94 Context Molecules

Supplementary Material for: "The Merck Molecular Force Field. II. MMFF94 van der Waals and Electrostatic Parameters for Intermolecular Interactions," T. A. Halgren, J. Comput. Chem., 17, 520-552 (1996).

As noted elsewhere [1], OPTIMOL allows a ligand to be modeled in a rigid enzyme "active site" in which the enzyme, or "context molecule" (CM), interacts with the ligand "subject molecule" (SM) only through nonbonded interactions. At present, a CM may contain one or several separate strands of peptide residues plus water(s) and any of several "protein-metal" cations. N- and C-termini in this representation are not "capped". All hydrogens must be supplied for heteroatoms but omitted from carbons. The listings below specify the MMFF atom types and partial atomic charges used for context-molecule atoms in computing nonbonded interactions. To the extent possible, these partial charges equal, or at least closely approximate, the values that would be generated from eq 7 by using the MMFF94 bond charge increments. Since a CM contains no hydrogens on carbon atoms, however, the partial charges for aromatic carbon atoms have been modified by adding the charge that would be assigned to hydrogen (e.g., +0.15) to that of the parent aromatic carbon. The van der Waals parameters are those for the associated MMFF94 atom type.

Listed in Table A1 are the residue types recognized by OPTIMOL/MMFF; both the chemical description and the three- or four-letter residue names used by OPTIMOL are shown. For the peptide residues, the parameters for C, O, N, HN and CA are the same as those used for ALA except, as explicitly noted, for PRO. MMFF also recognizes neutral (ORN) and protonated (ORNP) forms for ornithine; the parameters are as shown for LYS and LYSP except that the neutral CB-CG-CD chain in LYS and LYSP is reduced in length by one carbon. For water, the residue name may be WAT, HOH, or H2O, as shown; the names of the oxygen and hydrogen atoms must begin with "O" and "H", respectively, but otherwise are arbitrary. Finally, for the recognized protein metals, the residue names must be as shown below but the atom names are arbitrary.

Table A1. MMFF94 Atom Types and Partial Atomic Charges for Protein Residues Recognized for OPTIMOL/MMFF Context Molecules.

Alanine (ALA) 	
------------------------	
C	 3	 0.569	
O	 7	-0.570	
N	10	-0.730	
HN	28	 0.370	
CA	 1	 0.361	
CB	 1	 0.000	

Arginine (ARG) ------------------------ CB 1 0.000 CG 1 0.000 CD 1 0.369 NE 40 -0.819 HE 28 0.400 CZ 3 0.550 NH1 40 -0.850 HH11 28 0.400 HH12 28 0.400 NH2 9 -0.850 HH21 27 0.400

Arginine(+) (ARGP) ------------------------ CB 1 0.000 CG 1 0.000 CD 1 0.328 NE 56 -0.844 HE 36 0.450 CZ 57 1.200 NH1 56 -0.967 HH11 36 0.450 HH12 36 0.450 NH2 56 -0.967 HH21 36 0.450 HH22 36 0.450

Asparigine (ASN) ------------------------ CB 1 0.061 CG 3 0.569 OD1 7 -0.570 ND2 10 -0.800 HD1 28 0.370 HD2 28 0.370

Aspartic acid (ASP) ------------------------ CB 1 0.061 CG 3 0.659 OD1 7 -0.570 OD2 6 -0.650 HO 24 0.500

Aspartate (ASPN) ------------------------ CB 1 -0.106 CG 41 0.906 OD1 32 -0.900 OD2 32 -0.900

Cysteine (CYS) ------------------------ CB 1 0.230 SG 15 -0.230

Cysteine (CYSH) ------------------------ CB 1 0.230 SG 15 -0.410 HS 71 0.180

Glutamine (GLN) ------------------------ CB 1 0.000 CG 1 0.061 CD 3 0.569 OE1 7 -0.570 NE2 10 -0.800 HE1 28 0.370 HE2 28 0.370

Glutamic Acid (GLU) ------------------------ CB 1 0.000 CG 1 0.061 CD 3 0.659 OE1 7 -0.570 OE2 6 -0.650 HO 24 0.500

Glutamate (GLUN) ------------------------ CB 1 0.000 CG 1 -0.106 CD 41 0.906 OE1 32 -0.900 OE2 32 -0.900

Glycine (GLY) ------------------------ CA 1 0.361

Histidine(D) (HISD) ------------------------ CB 1 0.180 CG 63 -0.332 ND1 39 0.034 HD1 23 0.270 CD2 64 0.227 CE1 63 0.186 NE2 66 -0.565

Histidine(E) (HISE) ------------------------ CB 1 0.181 CG 64 0.046 ND1 66 -0.565 CD2 63 -0.152 CE1 63 0.186 NE2 39 0.034 HE2 23 0.270

Histidine(+) (HISP) ------------------------ CB 1 0.168 CG 78 0.182 ND1 81 -0.700 HD1 36 0.450 CD2 78 0.350 CE1 80 0.800 NE2 81 -0.700 HE2 36 0.450

Isoleucine (ILE) ------------------------ CB 1 0.000 CG1 1 0.000 CG2 1 0.000 CD1 1 0.000

Lysine (LYS) ------------------------ CB 1 0.000 CG 1 0.000 CD 1 0.000 CE 1 0.270 NZ 8 -0.990 HZ1 23 0.360 HZ2 23 0.360

Lysine(+) (LYSP) ------------------------ CB 1 0.000 CG 1 0.000 CD 1 0.000 CE 1 0.503 NZ 34 -0.853 HZ1 36 0.450 HZ2 36 0.450 HZ3 36 0.450

Methionine (MET) ------------------------ CB 1 0.000 CG 1 0.230 SD 15 -0.460 CE 1 0.230

Phenylalanine (PHE) ------------------------ CB 1 0.143 CG 37 -0.143 CD1 37 0.000 CD2 37 0.000 CE1 37 0.000 CE2 37 0.000 CZ 37 0.000

Proline (PRO) ------------------------ C 3 0.569 O 7 -0.570 N 10 -0.660 CA 1 0.361 CB 1 0.000 CG 1 0.000 CD 1 0.300

Serine (SER) ------------------------ CB 1 0.280 OG 6 -0.680 HO 21 0.400

Threonine (THR) ------------------------ CB 1 0.280 OG1 6 -0.680 HO 21 0.400 CG2 1 0.000

Tryptophan (TRP) ------------------------ CB 1 0.181 CG 64 -0.181 CD1 63 -0.152 CD2 64 0.000 NE1 39 0.034 HE1 23 0.270 CE2 63 -0.152 CE3 37 0.000 CZ2 37 0.000 CZ3 37 0.000 CH2 37 0.000

Tyrosine (TYR) ------------------------ CB 1 0.143 CG 37 -0.143 CD1 37 0.000 CD2 37 0.000 CE1 37 0.000 CE2 37 0.000 CZ 37 0.083 OH 6 -0.533 HO 29 0.450

Valine (VAL) ------------------------ CB 1 0.000 CG1 1 0.000 CG2 1 0.000

Water (WAT, HOH or H2O) -------------------------------- O* 70 -0.860 H* 31 0.430 H* 31 0.430

Fe[2+] (FE2) ------------------------ 87 2.000

Fe[3+] (FE3) ------------------------ 88 3.000

F[-] (FM) ------------------------ 89 -1.000

Cl[-] (CLM) ------------------------ 90 -1.000

Br[-] (BRM) ------------------------ 91 -1.000

Li[+] (LIP) ------------------------ 92 1.000

Na[+] (NAP) ------------------------ 93 1.000

K[+] (KP) ------------------------ 94 1.000

Zn[2+] (ZN or ZIN) ------------------------ 95 2.000

Ca[2+] (CAL or CA) ------------------------ 96 2.000

Cu[1+] (CU1) ------------------------ 97 1.000

Cu[2+] (CU2 or CU) ------------------------ 98 2.000

Mg[2+] (MG2) ------------------------ 99 2.000


[1] M. K. Holloway, J. M. Wai, T. A. Halgren, P. M. D. Fitzgerald, J. P. Vacca, B. D. Dorsey, R. B. Levin, W. J. Thompson, L. J. Chen, S. J. deSolms, N. Gaffin, A. K. Ghosh, E. A. Giuliani, S. L. Graham, J. P. Guare, R. W. Hungate, T. A. Lyle, W. M. Sanders, T. J. Tucker, M. Wiggins, C. M. Wiscount, O. W. Woltersdorf, S. D. Young, P. L. Darke, and J. A. Zugay, J. Med. Chem., 38, 305-317 (1995).