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1// nx_chem_descriptors_test.nx -- C2.7 KAT for HBD/HBA/rotatable 2// bonds + partial Lipinski + partial Veber. 3// 4// expect_exit: 0 5// 6// license_tier: ORIGINAL 7 8import "nx_chem.nx" 9import "nx_chem_molecule.nx" 10import "nx_chem_smiles.nx" 11import "nx_chem_periodic.nx" 12import "nx_chem_valence.nx" 13import "nx_chem_descriptors.nx" 14 15// Helper: parse + populate implicit H + perceive rings + return MolGraph 16func parse_with_h(src: *u8, n: nx_int) -> *MolGraph { 17 let m: *MolGraph = nx_chem_parse_smiles(src, n) 18 let _f: nx_int = nx_chem_compute_implicit_h(m) 19 let _r: nx_int = nx_chem_descriptors_perceive_rings(m) 20 return m 21} 22 23// ================================================================= 24// A -- water "O": HBD=2 (2 H on O), HBA=1 (1 O) 25// ================================================================= 26func a_water() -> nx_int { 27 let s: *u8 = sys_mmap(8); s[0] = 0x4F 28 let m: *MolGraph = parse_with_h(s, 1) 29 if nx_chem_count_hbd(m) != 2 { return 11 } 30 if nx_chem_count_hba(m) != 1 { return 12 } 31 if nx_chem_count_rotatable_bonds(m) != 0 { return 13 } 32 if nx_chem_count_aromatic_atoms(m) != 0 { return 14 } 33 return 0 34} 35 36// ================================================================= 37// B -- methane "C": HBD=0 (no N/O/S), HBA=0 38// ================================================================= 39func b_methane() -> nx_int { 40 let s: *u8 = sys_mmap(8); s[0] = 0x43 41 let m: *MolGraph = parse_with_h(s, 1) 42 if nx_chem_count_hbd(m) != 0 { return 21 } 43 if nx_chem_count_hba(m) != 0 { return 22 } 44 if nx_chem_count_rotatable_bonds(m) != 0 { return 23 } 45 return 0 46} 47 48// ================================================================= 49// C -- ethanol "CCO": HBD=1 (OH), HBA=1 (O), rotatable=0 50// C-C bond: connects deg-1 C (terminal) to deg-2 C; one end terminal -> not rotatable 51// C-O bond: connects deg-2 C to deg-1 O; one end terminal -> not rotatable 52// ================================================================= 53func c_ethanol() -> nx_int { 54 let s: *u8 = sys_mmap(8) 55 s[0] = 0x43; s[1] = 0x43; s[2] = 0x4F 56 let m: *MolGraph = parse_with_h(s, 3) 57 if nx_chem_count_hbd(m) != 1 { return 31 } 58 if nx_chem_count_hba(m) != 1 { return 32 } 59 if nx_chem_count_rotatable_bonds(m) != 0 { return 33 } 60 if nx_chem_count_heavy_atoms(m) != 3 { return 34 } 61 return 0 62} 63 64// ================================================================= 65// D -- methylamine "CN": HBD=2 (NH2), HBA=1 (N) 66// ================================================================= 67func d_methylamine() -> nx_int { 68 let s: *u8 = sys_mmap(8) 69 s[0] = 0x43; s[1] = 0x4E 70 let m: *MolGraph = parse_with_h(s, 2) 71 if nx_chem_count_hbd(m) != 2 { return 41 } 72 if nx_chem_count_hba(m) != 1 { return 42 } 73 return 0 74} 75 76// ================================================================= 77// E -- ethylamine "CCN": rotatable bond count. 78// Atoms: C(deg=1), C(deg=2), N(deg=1). 79// C-C: deg-1 to deg-2 (one terminal); not rotatable. 80// C-N: deg-2 to deg-1 (one terminal); not rotatable. 81// Expected: 0 rotatable. 82// ================================================================= 83func e_ethylamine_rot() -> nx_int { 84 let s: *u8 = sys_mmap(8) 85 s[0] = 0x43; s[1] = 0x43; s[2] = 0x4E 86 let m: *MolGraph = parse_with_h(s, 3) 87 if nx_chem_count_rotatable_bonds(m) != 0 { return 51 } 88 return 0 89} 90 91// ================================================================= 92// F -- propyl amine "CCCN": rotatable bond count. 93// Atoms: C0(deg=1), C1(deg=2), C2(deg=2), N(deg=1). 94// C0-C1: terminal end -> not rotatable. 95// C1-C2: deg-2 to deg-2; NOT terminal AND NOT in ring AND single -> rotatable! (1) 96// C2-N: deg-2 to deg-1; terminal -> not rotatable. 97// Expected: 1 rotatable bond. 98// ================================================================= 99func f_propylamine_rot() -> nx_int { 100 let s: *u8 = sys_mmap(8) 101 s[0] = 0x43; s[1] = 0x43; s[2] = 0x43; s[3] = 0x4E 102 let m: *MolGraph = parse_with_h(s, 4) 103 if nx_chem_count_rotatable_bonds(m) != 1 { return 61 } 104 return 0 105} 106 107// ================================================================= 108// G -- benzene "c1ccccc1": HBD=0, HBA=0, rotatable=0 (all aromatic), 109// aromatic_atoms=6, approx_aromatic_rings=1 110// ================================================================= 111func g_benzene() -> nx_int { 112 let s: *u8 = sys_mmap(16) 113 s[0] = 0x63; s[1] = 0x31 114 s[2] = 0x63; s[3] = 0x63 115 s[4] = 0x63; s[5] = 0x63 116 s[6] = 0x63; s[7] = 0x31 117 let m: *MolGraph = parse_with_h(s, 8) 118 if nx_chem_count_hbd(m) != 0 { return 71 } 119 if nx_chem_count_hba(m) != 0 { return 72 } 120 if nx_chem_count_rotatable_bonds(m) != 0 { return 73 } 121 if nx_chem_count_aromatic_atoms(m) != 6 { return 74 } 122 if nx_chem_approx_aromatic_rings(m) != 1 { return 75 } 123 return 0 124} 125 126// ================================================================= 127// H -- cyclohexane "C1CCCCC1": HBD=0, HBA=0, rotatable=0 128// (all bonds in ring), aromatic_atoms=0 129// ================================================================= 130func h_cyclohexane() -> nx_int { 131 let s: *u8 = sys_mmap(16) 132 s[0] = 0x43; s[1] = 0x31 133 s[2] = 0x43; s[3] = 0x43 134 s[4] = 0x43; s[5] = 0x43 135 s[6] = 0x43; s[7] = 0x31 136 let m: *MolGraph = parse_with_h(s, 8) 137 if nx_chem_count_hbd(m) != 0 { return 81 } 138 if nx_chem_count_hba(m) != 0 { return 82 } 139 if nx_chem_count_rotatable_bonds(m) != 0 { return 83 } 140 if nx_chem_count_aromatic_atoms(m) != 0 { return 84 } 141 return 0 142} 143 144// ================================================================= 145// I -- Lipinski Ro5 partial PASS for small drug-like molecule. 146// Ethanol "CCO": MW=46.069 (< 500), HBD=1 (<= 5), HBA=1 (<= 10). 147// Zero violations -> pass. 148// ================================================================= 149func i_lipinski_ethanol_pass() -> nx_int { 150 let table: *Element = nx_chem_periodic_table_118() 151 let s: *u8 = sys_mmap(8) 152 s[0] = 0x43; s[1] = 0x43; s[2] = 0x4F 153 let m: *MolGraph = parse_with_h(s, 3) 154 if nx_chem_lipinski_ro5_partial(m, table) != 1 { return 91 } 155 return 0 156} 157 158// ================================================================= 159// J -- Lipinski Ro5 FAIL on extreme HBA count. 160// Construct a molecule with many oxygens. "OOOOOOOOOOOOOOOOOO" has 161// 18 O atoms (HBA=18 > 10). HBDs = 36 (each O has 2 implicit Hs; 162// but with peroxide-like O-O chain, each internal O has 0 H, only 163// terminal O have H). Actually for the "OOOOO..." chain each O has 164// deg 1 or 2 -- internal O has deg 2 (uses both valences) so h=0; 165// terminal O has deg 1 so h=1. 166// For 18 O atoms in a chain: 2 terminal (h=1 each) + 16 internal 167// (h=0) -> HBD=2, HBA=18 (>10) -> 1 violation, still passes Ro5. 168// 169// Better fail-case: many HBDs. Use 12 explicit-H bracket-N atoms 170// "[NH3]" chained: each contributes 3 HBDs. But chaining 12 [NH3] 171// would be ridiculous valence; let me just test that the COUNT 172// works correctly with a known peroxide chain. 173// "OO" (peroxide): 2 O atoms each with deg=1 -> h=1 each -> HBD=2, HBA=2. 174// ================================================================= 175func j_peroxide() -> nx_int { 176 let table: *Element = nx_chem_periodic_table_118() 177 let s: *u8 = sys_mmap(8) 178 s[0] = 0x4F; s[1] = 0x4F 179 let m: *MolGraph = parse_with_h(s, 2) 180 if nx_chem_count_hbd(m) != 2 { return 101 } 181 if nx_chem_count_hba(m) != 2 { return 102 } 182 if nx_chem_lipinski_ro5_partial(m, table) != 1 { return 103 } // small mol passes 183 return 0 184} 185 186// ================================================================= 187// K -- Veber partial PASS for ethanol (0 rotatable bonds). 188// ================================================================= 189func k_veber_ethanol_pass() -> nx_int { 190 let s: *u8 = sys_mmap(8) 191 s[0] = 0x43; s[1] = 0x43; s[2] = 0x4F 192 let m: *MolGraph = parse_with_h(s, 3) 193 if nx_chem_veber_partial(m) != 1 { return 111 } 194 return 0 195} 196 197// ================================================================= 198// L -- heavy atom count: ethanol "CCO" has 3 heavy atoms. 199// ================================================================= 200func l_heavy_atom_count() -> nx_int { 201 let s: *u8 = sys_mmap(8) 202 s[0] = 0x43; s[1] = 0x43; s[2] = 0x4F 203 let m: *MolGraph = parse_with_h(s, 3) 204 if nx_chem_count_heavy_atoms(m) != 3 { return 121 } 205 return 0 206} 207 208// ================================================================= 209// M -- bracket atoms preserved: "[NH4+]" has 4 H, charge +1. 210// HBD=0 (N with charge > 0 still has 4 H; but N+ is conventionally 211// excluded from HBA, and HBD here = 4 since N still donates). 212// Actually Lipinski counts NH4+ Hs as HBDs (any X-H where X is N/O/S). 213// And HBA: my impl excludes N+ from HBA (charge > 0 -> no HBA). 214// So [NH4+]: HBD=4, HBA=0. 215// ================================================================= 216func m_ammonium() -> nx_int { 217 let s: *u8 = sys_mmap(16) 218 s[0] = 0x5B; s[1] = 0x4E; s[2] = 0x48; s[3] = 0x34; s[4] = 0x2B; s[5] = 0x5D 219 let m: *MolGraph = parse_with_h(s, 6) 220 if nx_chem_count_hbd(m) != 4 { return 131 } 221 if nx_chem_count_hba(m) != 0 { return 132 } 222 return 0 223} 224 225// ================================================================= 226// N -- hydrogen peroxide rotatable bond: O-O in "OO" is between two 227// deg-1 terminal oxygens -> NOT rotatable per Veber definition. 228// ================================================================= 229func n_peroxide_rot() -> nx_int { 230 let s: *u8 = sys_mmap(8) 231 s[0] = 0x4F; s[1] = 0x4F 232 let m: *MolGraph = parse_with_h(s, 2) 233 if nx_chem_count_rotatable_bonds(m) != 0 { return 141 } 234 return 0 235} 236 237func main() -> nx_exit { 238 println("=== nx_chem_descriptors -- C2.7 KAT: HBD/HBA/rotatable/Lipinski/Veber ===" as *u8) 239 240 let ra: nx_int = a_water() 241 if ra != 0 { println("A water FAIL" as *u8); return ra } 242 println("A water PASS O -> HBD=2 / HBA=1 / rot=0 / arom=0" as *u8) 243 244 let rb: nx_int = b_methane() 245 if rb != 0 { println("B methane FAIL" as *u8); return rb } 246 println("B methane PASS C -> HBD=0 / HBA=0 / rot=0" as *u8) 247 248 let rc: nx_int = c_ethanol() 249 if rc != 0 { println("C ethanol FAIL" as *u8); return rc } 250 println("C ethanol PASS CCO -> HBD=1 / HBA=1 / rot=0 / heavy=3" as *u8) 251 252 let rd: nx_int = d_methylamine() 253 if rd != 0 { println("D methylamine FAIL" as *u8); return rd } 254 println("D methylamine PASS CN -> HBD=2 / HBA=1" as *u8) 255 256 let re: nx_int = e_ethylamine_rot() 257 if re != 0 { println("E ethylamine_rot FAIL" as *u8); return re } 258 println("E ethylamine_rot PASS CCN -> 0 rotatable bonds (both ends terminal)" as *u8) 259 260 let rf: nx_int = f_propylamine_rot() 261 if rf != 0 { println("F propylamine_rot FAIL" as *u8); return rf } 262 println("F propylamine_rot PASS CCCN -> 1 rotatable bond (internal C-C; deg=2 to deg=2)" as *u8) 263 264 let rg: nx_int = g_benzene() 265 if rg != 0 { println("G benzene FAIL" as *u8); return rg } 266 println("G benzene PASS c1ccccc1 -> arom_atoms=6 / approx_arom_rings=1" as *u8) 267 268 let rh: nx_int = h_cyclohexane() 269 if rh != 0 { println("H cyclohexane FAIL" as *u8); return rh } 270 println("H cyclohexane PASS C1CCCCC1 -> rot=0 (all ring bonds) / arom=0" as *u8) 271 272 let ri: nx_int = i_lipinski_ethanol_pass() 273 if ri != 0 { println("I lipinski_ethanol_pass FAIL" as *u8); return ri } 274 println("I lipinski_ethanol PASS CCO satisfies Ro5 partial (MW 46 / HBD 1 / HBA 1)" as *u8) 275 276 let rj: nx_int = j_peroxide() 277 if rj != 0 { println("J peroxide FAIL" as *u8); return rj } 278 println("J peroxide PASS OO -> HBD=2 / HBA=2; Ro5 partial passes" as *u8) 279 280 let rk: nx_int = k_veber_ethanol_pass() 281 if rk != 0 { println("K veber_ethanol_pass FAIL" as *u8); return rk } 282 println("K veber_ethanol PASS CCO satisfies Veber partial (rot 0 <= 10)" as *u8) 283 284 let rl: nx_int = l_heavy_atom_count() 285 if rl != 0 { println("L heavy_atom_count FAIL" as *u8); return rl } 286 println("L heavy_atom_count PASS CCO -> 3 heavy atoms" as *u8) 287 288 let rm: nx_int = m_ammonium() 289 if rm != 0 { println("M ammonium FAIL" as *u8); return rm } 290 println("M ammonium PASS [NH4+] -> HBD=4 / HBA=0 (N+ excluded from HBA)" as *u8) 291 292 let rn: nx_int = n_peroxide_rot() 293 if rn != 0 { println("N peroxide_rot FAIL" as *u8); return rn } 294 println("N peroxide_rot PASS OO -> 0 rotatable bonds (both terminal)" as *u8) 295 296 println("" as *u8) 297 println("=== C2.7 substrate milestone PASS ===" as *u8) 298 println(" descriptors : HBD (N/O/S with H) / HBA (N+/O excluded) / rotatable bonds" as *u8) 299 println(" (single, not-in-ring, non-terminal heavy atoms) / aromatic" as *u8) 300 println(" atoms + approx ring count (assumes 6-membered)" as *u8) 301 println(" Lipinski Ro5 partial: MW + HBD + HBA components; <=1 violation -> pass" as *u8) 302 println(" Veber partial : rotatable bonds <= 10" as *u8) 303 println(" honest gaps : logP via Crippen-Wildman atom-type table (C2.8); TPSA via" as *u8) 304 println(" Ertl atom-contribution table (C2.8); SSSR proper ring" as *u8) 305 println(" perception (C2.7.1); PAINS structural alerts (C2.9)" as *u8) 306 println(" next : C2.8 -- logP + TPSA atom-contribution tables (full Ro5/Veber)" as *u8) 307 return 0 308}