m3triq 0.2.2 → 0.2.4

package/dist/cli.js

@@ -23,7 +23,7 @@ const program = new Command();
 program
     .name('m3t')
     .description('M3TRIQ — protein-ligand analysis from the terminal')
-    .version('0.2.2')
+    .version('0.2.4')
     .option('--json', 'Output as JSON (machine-readable)')
     .hook('preAction', (thisCommand) => {
     const opts = thisCommand.optsWithGlobals();

package/dist/commands/docking.js

@@ -27,19 +27,112 @@ function parseCompoundsFile(filePath) {
         };
     });
 }
-/** Resolve PDB argument: if it's a file path, read content; otherwise return as-is (PDB ID). */
-function resolvePdb(pdb) {
+/**
+ * Resolve PDB argument to file content.
+ * - existing file path → read it
+ * - 4-letter PDB ID (e.g. "3HTB") → fetch from RCSB
+ * - anything else (assume raw PDB text already) → return as-is
+ */
+async function resolvePdb(pdb) {
     if (fs.existsSync(pdb)) {
         return { content: fs.readFileSync(pdb, 'utf-8'), label: pdb.split('/').pop() || pdb };
     }
+    if (/^[0-9A-Za-z]{4}$/.test(pdb)) {
+        const id = pdb.toUpperCase();
+        const res = await fetch(`https://files.rcsb.org/download/${id}.pdb`);
+        if (!res.ok) {
+            throw new Error(`PDB '${id}' not found at RCSB (HTTP ${res.status}). ` +
+                `Check the ID at https://rcsb.org/structure/${id} or pass a local .pdb file.`);
+        }
+        return { content: await res.text(), label: id };
+    }
     return { content: pdb, label: pdb };
 }
-/** Shared binding site options for site-directed docking (Vina/GNINA) */
+// HETATM residues that are not real ligands — waters, ions, common cryoprotectants
+// and buffer components. Excluded from auto binding-site detection.
+const FILLER_HETATMS = new Set([
+    'HOH', 'WAT', 'DOD', 'D2O',
+    'NA', 'CL', 'K', 'BR', 'I', 'F', 'MG', 'CA', 'ZN', 'FE', 'MN', 'CU', 'NI', 'CO', 'CD', 'HG', 'PB', 'BA', 'CS', 'SR',
+    'SO4', 'PO4', 'BO3', 'NO3', 'CO3', 'HCO3', 'OH', 'OXY', 'PER', 'SUL', 'MOO',
+    'GOL', 'EDO', 'PEG', 'PG4', 'PE4', 'PGE', 'MPD', 'BME', 'DTT', 'MRD', 'BU3', 'P6G', 'BTB', 'EPE', 'HEPES',
+    'TRS', 'TRIS', 'ACT', 'ACE', 'FMT', 'EOH', 'IPA', 'DMS', 'DMF', 'MES', 'BES', 'GLY', 'CIT', 'MLT', 'TLA',
+    'NH4', 'PYR', 'HED', 'BNG', 'LMT', 'OLA', 'OLB', 'OLC',
+]);
+/** Find the largest non-filler HETATM residue and return its centroid. Returns null if none. */
+function autoDetectSite(pdbContent) {
+    const groups = new Map();
+    for (const line of pdbContent.split('\n')) {
+        if (!line.startsWith('HETATM'))
+            continue;
+        const resname = line.slice(17, 20).trim();
+        if (FILLER_HETATMS.has(resname.toUpperCase()))
+            continue;
+        const chain = line.slice(21, 22).trim() || ' ';
+        const resnum = parseInt(line.slice(22, 26).trim(), 10);
+        const x = parseFloat(line.slice(30, 38));
+        const y = parseFloat(line.slice(38, 46));
+        const z = parseFloat(line.slice(46, 54));
+        if (!Number.isFinite(x) || !Number.isFinite(y) || !Number.isFinite(z))
+            continue;
+        const key = `${resname}|${chain}|${resnum}`;
+        let g = groups.get(key);
+        if (!g) {
+            g = { resname, chain, resnum, xs: [], ys: [], zs: [] };
+            groups.set(key, g);
+        }
+        g.xs.push(x);
+        g.ys.push(y);
+        g.zs.push(z);
+    }
+    let best = null;
+    for (const g of groups.values()) {
+        if (!best || g.xs.length > best.xs.length)
+            best = g;
+    }
+    // A real ligand has ≥5 heavy atoms; anything smaller is likely a stray modification.
+    if (!best || best.xs.length < 5)
+        return null;
+    const n = best.xs.length;
+    const mean = (a) => Math.round((a.reduce((s, v) => s + v, 0) / n) * 1000) / 1000;
+    return {
+        resname: best.resname, chain: best.chain, resnum: best.resnum,
+        center: { x: mean(best.xs), y: mean(best.ys), z: mean(best.zs) },
+        atomCount: n,
+    };
+}
+/**
+ * Resolve the binding site for a docking job.
+ * Throws on explicit (0,0,0) (a known agent placeholder). When any coord is
+ * missing, runs autoDetectSite() on the PDB content; logs what was picked to
+ * stderr so the agent sees the decision.
+ */
+function resolveSite(pdbContent, pdbLabel, cx, cy, cz) {
+    const allSet = [cx, cy, cz].every(v => typeof v === 'number' && !Number.isNaN(v));
+    const allZero = allSet && cx === 0 && cy === 0 && cz === 0;
+    if (allZero) {
+        throw new Error(`Binding site (0,0,0) is not a valid center. To find real coordinates, ` +
+            `check the co-crystallized ligand at https://rcsb.org/structure/${pdbLabel}/ligands, ` +
+            `or omit --cx/--cy/--cz to auto-detect from the PDB.`);
+    }
+    if (allSet)
+        return { x: cx, y: cy, z: cz };
+    const site = autoDetectSite(pdbContent);
+    if (!site) {
+        throw new Error(`Could not auto-detect a binding site in ${pdbLabel} (no co-crystallized ligand ` +
+            `with ≥5 heavy atoms). Specify --cx/--cy/--cz manually — check ligands at ` +
+            `https://rcsb.org/structure/${pdbLabel}/ligands.`);
+    }
+    process.stderr.write(`Auto-detected binding site at HETATM ${site.resname} ${site.chain}${site.resnum} ` +
+        `(${site.atomCount} atoms): center=(${site.center.x}, ${site.center.y}, ${site.center.z})\n`);
+    return site.center;
+}
+/** Shared binding site options for site-directed docking (Vina/GNINA).
+ *  Coords are OPTIONAL — if omitted, the CLI auto-detects from the PDB. */
 function addSiteOptions(cmd) {
     return cmd
-        .requiredOption('--cx <x>', 'Binding site center X', parseFloat)
-        .requiredOption('--cy <y>', 'Binding site center Y', parseFloat)
-        .requiredOption('--cz <z>', 'Binding site center Z', parseFloat)
+        .option('--cx <x>', 'Binding site center X (omit to auto-detect)', parseFloat)
+        .option('--cy <y>', 'Binding site center Y (omit to auto-detect)', parseFloat)
+        .option('--cz <z>', 'Binding site center Z (omit to auto-detect)', parseFloat)
         .option('--sx <x>', 'Search box size X (default: 20)', parseFloat)
         .option('--sy <y>', 'Search box size Y (default: 20)', parseFloat)
         .option('--sz <z>', 'Search box size Z (default: 20)', parseFloat);
@@ -73,7 +166,7 @@ export function registerDockingCommands(program) {
         const project = requireProject();
         const client = createClient();
         const consoleUrl = getConsoleUrl();
-        const { content: pdbContent } = resolvePdb(pdb);
+        const { content: pdbContent } = await resolvePdb(pdb);
         const result = await client.createDiffDockJob({
             project_id: project.id,
             ligand_smiles: smiles,
@@ -106,7 +199,8 @@ async function runSiteDock(smiles, pdb, method, opts) {
     const project = requireProject();
     const client = createClient();
     const consoleUrl = getConsoleUrl();
-    const { content: pdbContent, label: pdbLabel } = resolvePdb(pdb);
+    const { content: pdbContent, label: pdbLabel } = await resolvePdb(pdb);
+    const site = resolveSite(pdbContent, pdbLabel, opts.cx, opts.cy, opts.cz);
     const title = `Dock ${smiles.substring(0, 30)} → ${pdbLabel}`;
     const result = await client.createDockingJob({
         project_id: project.id,
@@ -115,9 +209,9 @@ async function runSiteDock(smiles, pdb, method, opts) {
         ligand_smiles: smiles,
         scoring_function: method,
         exhaustiveness: opts.exhaustiveness,
-        center_x: opts.cx,
-        center_y: opts.cy,
-        center_z: opts.cz,
+        center_x: site.x,
+        center_y: site.y,
+        center_z: site.z,
         size_x: opts.sx,
         size_y: opts.sy,
         size_z: opts.sz,
@@ -133,7 +227,8 @@ async function runBatchDock(file, pdb, method, opts) {
     const client = createClient();
     const consoleUrl = getConsoleUrl();
     const compounds = parseCompoundsFile(file);
-    const { content: pdbContent, label: pdbLabel } = resolvePdb(pdb);
+    const { content: pdbContent, label: pdbLabel } = await resolvePdb(pdb);
+    const site = resolveSite(pdbContent, pdbLabel, opts.cx, opts.cy, opts.cz);
     const title = `Batch ${method.toUpperCase()} ${compounds.length} compounds → ${pdbLabel}`;
     const result = await client.createBatchDockingJob({
         project_id: project.id,
@@ -141,9 +236,9 @@ async function runBatchDock(file, pdb, method, opts) {
         protein_pdb: pdbContent,
         ligand_smiles_list: compounds.map(c => c.smiles),
         scoring_function: method,
-        center_x: opts.cx,
-        center_y: opts.cy,
-        center_z: opts.cz,
+        center_x: site.x,
+        center_y: site.y,
+        center_z: site.z,
         size_x: opts.sx,
         size_y: opts.sy,
         size_z: opts.sz,

package/package.json

@@ -1,6 +1,6 @@
 {
   "name": "m3triq",
-  "version": "0.2.2",
+  "version": "0.2.4",
   "description": "M3TRIQ — protein-ligand analysis from the terminal",
   "type": "module",
   "bin": {