@datagrok/sequence-translator 1.5.3 → 1.6.1

package/src/polytool/conversion/pt-chain.ts

@@ -1,663 +1,66 @@
-import {Atom, IHelmBio, HelmMol, HelmType, JSDraw2ModuleType, OrgType} from '@datagrok-libraries/bio/src/helm/types';
 import {IHelmHelper} from '@datagrok-libraries/bio/src/helm/helm-helper';
-import {HelmTypes} from '@datagrok-libraries/bio/src/helm/consts';
-import {cleanupHelmSymbol} from '@datagrok-libraries/bio/src/helm/utils';
+import {Linkage} from './pt-misc';
+import {Rules} from './pt-rules';
+import {HelmMol} from '@datagrok-libraries/bio/src/helm/types';
+import {fromObjectsToHelm, handleDuplicated, handleLinkRules,
+  handleReactionRules, parseHelm, parseSeparator} from './pt-tools-parse';
+import {getHelmMol, helmMolToNotation} from './pt-tools-helmmol';
 
-import {getOuterIdx, getInnerIdx} from './pt-misc';
-import {Rules, RuleLink, RuleReaction, getMonomerPairs} from './pt-rules';
-
-declare const JSDraw2: JSDraw2ModuleType;
-declare const org: OrgType;
-
-type Linkage = {
-  fChain: number,
-  sChain: number,
-  /** Continuous 1-based numbering */ fMonomer: number,
-  /** Continuous 1-based numbering */ sMonomer: number,
-  fR: number,
-  sR: number
-}
-export type PtBio = IHelmBio & { i: number, j: number };
-
-type PtAtom = Atom<HelmType, PtBio>
 
 export class Chain {
   linkages: Linkage[];
   monomers: string[][];
   mol: HelmMol;
 
-  constructor(
-    monomers: string[][], linkages: Linkage[], mol: HelmMol,
-    protected helmHelper: IHelmHelper,
-  ) {
+  underRules: boolean = false;
+  linkagesUnderRules: Linkage[];
+  monomersUnderRules: string[][];
+  molUnderRules: HelmMol;
+
+  constructor(monomers: string[][], linkages: Linkage[], protected helmHelper: IHelmHelper) {
     this.linkages = linkages;
     this.monomers = monomers;
-    this.mol = mol;
-  }
-
-  /** Parse harmonized sequence (template) from pseudo helm */
-  static parseHelm(helm: string, helmHelper: IHelmHelper) {
-    const ea = /(\w+\{.*\})\$(.*)\$(.*)\$(.*)\$/g.exec(helm)!;
-    // const fragmentation = helm.split('$');
-    const fragmentation = [ea[1], ea[2], ea[3], ea[4]];
-
-    const rawFragments = fragmentation[0].split('|');
-    const rawLinkages = fragmentation[1].split('|');
-
-    const monomers = new Array<Array<string>>(rawFragments.length);
-    const linkages: Linkage[] = [];
-
-    const resHwe = helmHelper.createHelmWebEditor();
-    const resMol = resHwe.editor.m;
-
-    let counter = 0;
-    const p = new JSDraw2.Point(0, 0);
-    //HELM parsing
-    for (let i = 0; i < rawFragments.length; i++) {
-      const idxStart = rawFragments[i].indexOf('{');
-      const idxEnd = rawFragments[i].indexOf('}');
-
-      monomers[i] = rawFragments[i].slice(idxStart + 1, idxEnd).split('.').map((s) => cleanupHelmSymbol(s));
-      for (let j = 0; j < monomers[i].length; j++) {
-        const elem = monomers[i][j];
-        const bio: PtBio = {type: HelmTypes.AA, i: i, j: j, continuousId: counter};
-        const atom = new JSDraw2.Atom<HelmType, IHelmBio>(p, elem, bio);
-        resMol.addAtom(atom);
-
-        if (j !== 0) {
-          const atom1 = resMol.atoms[counter - 1];
-          const atom2 = resMol.atoms[counter];
-          const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-          bond.r1 = 2;
-          bond.r2 = 1;
-          resMol.addBond(bond);
-        }
-
-        counter++;
-        p.x += JSDraw2.Editor.BONDLENGTH; // Inspired by HELMWebEditor
-      }
-      p.y += 4 * JSDraw2.Editor.BONDLENGTH; // Inspired by HELMWebEditor
-    }
-
-    //HELM parsing
-    for (let i = 0; i < rawLinkages.length; i++) {
-      if (rawLinkages[i] !== '' && rawLinkages[i] !== 'V2.0') {
-        const rawData = rawLinkages[i].split(',');
-        const fChainIdx = parseInt(rawData[0].replace('PEPTIDE', '')) - 1;
-        const sChainIdx = parseInt(rawData[1].replace('PEPTIDE', '')) - 1;
-        const rawDataConnections = rawData[2].split('-');
-        const rawDataConnection1 = rawDataConnections[0].split(':');
-        const rawDataConnection2 = rawDataConnections[1].split(':');
-
-        linkages.push({
-          fChain: fChainIdx,
-          sChain: sChainIdx,
-          fMonomer: getOuterIdx(parseInt(rawDataConnection1[0]), fChainIdx, monomers),
-          sMonomer: getOuterIdx(parseInt(rawDataConnection2[0]), sChainIdx, monomers),
-          fR: parseInt(rawDataConnection1[1].replace('R', '')),
-          sR: parseInt(rawDataConnection2[1].replace('R', '')),
-        });
-      }
-    }
-
-    for (let i = 0; i < linkages.length; i++) {
-      const atom1 = resMol.atoms[linkages[i].fMonomer - 1];
-      const atom2 = resMol.atoms[linkages[i].sMonomer - 1];
-      const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-      bond.r1 = linkages[i].fR;
-      bond.r2 = linkages[i].sR;
-      resMol.addBond(bond);
-    }
-
-    return new Chain(monomers, linkages, resMol, helmHelper);
-  }
-
-  /** Get macromolecule from harmonized sequence (template) */
-  applyRules(rules: Rules): Chain {
-    const newNotation = this.getNotation();
-    return Chain.fromNotation(newNotation, rules, this.helmHelper);
+    this.mol = getHelmMol(linkages, monomers, helmHelper);
   }
 
-  static fromNotation(sequence: string, rules: Rules, helmHelper: IHelmHelper): Chain {
-    const heterodimerCode = rules.heterodimerCode;
-    const homodimerCode = rules.homodimerCode;
-
-    const mainFragments: string[] = [];
-    const linkages: Linkage[] = [];
-
-    //NOTICE: this works only with simple single heterodimers
-    const heterodimeric = heterodimerCode !== null ? sequence.split(`(${rules.heterodimerCode!})`) : '';
-    if (heterodimerCode !== null && heterodimeric.length > 1) {
-      linkages.push({fChain: 0, sChain: 1, fMonomer: 1, sMonomer: 1, fR: 1, sR: 1});
-      mainFragments.push(heterodimeric[1].replaceAll('{', '').replaceAll('}', ''));
-      mainFragments.push(heterodimeric[2].replaceAll('{', '').replaceAll('}', ''));
-    } else {
-      mainFragments.push(sequence);
-    }
-
-    //NOTICE: this works only with simple single dimers
-    for (let i = 0; i < mainFragments.length; i++) {
-      if (homodimerCode !== null && mainFragments[i].includes(`(${homodimerCode!})`)) {
-        const idxSequence = mainFragments.length;
-
-        linkages.push({fChain: i, sChain: idxSequence, fMonomer: 1, sMonomer: 1, fR: 1, sR: 1});
-        const rawDimer = mainFragments[i].replace(`(${homodimerCode!})`, '');
-        const idx = rawDimer.indexOf('{');
-        const linker = rawDimer.slice(0, idx);
-        const body = rawDimer.replace(linker, '').replaceAll('{', '').replaceAll('}', '');
-
-        mainFragments[i] = linker + body;
-        mainFragments.push(body);
-      }
-    }
-
-    for (let i = 0; i < mainFragments.length; i++) {
-      if (homodimerCode !== null && mainFragments[i].includes(`(${homodimerCode!})`)) {
-        const idxSequence = mainFragments.length;
-
-        linkages.push({fChain: i, sChain: idxSequence, fMonomer: 1, sMonomer: 1, fR: 1, sR: 1});
-        const rawDimer = mainFragments[i].replace(`(${homodimerCode!})`, '');
-        const idx = rawDimer.indexOf('{');
-        const linker = rawDimer.slice(0, idx);
-        const body = rawDimer.replace(linker, '').replaceAll('{', '').replaceAll('}', '');
-
-        mainFragments[i] = linker + body;
-        mainFragments.push(body);
-      }
-    }
-
-    const monomers = new Array<Array<string>>(mainFragments.length);
-
-    for (let i = 0; i < mainFragments.length; i++) {
-      const rawMonomers = mainFragments[i].split('-');
-      const linkedPositions = this.getLinkedPositions(rawMonomers, rules.linkRules);
-      const [monomersCycled, allPos1, allPos2, allAttaches1, allAttaches2] =
-        this.getAllCycles(rules.linkRules, rawMonomers, linkedPositions);
-
-      const monomersReady = new Array<string>(monomersCycled.length);
-      // for (let j = 0; j < monomersCycled.length; j++)
-      //   monomersReady[j] = `[${monomersCycled[j]}]`;
-
-      for (let j = 0; j < allPos1.length; j++) {
-        linkages.push({
-          fChain: i,
-          sChain: i,
-          fMonomer: allPos1[j],
-          sMonomer: allPos2[j],
-          fR: allAttaches1[j],
-          sR: allAttaches2[j],
-        });
-      }
-
-      monomers[i] = monomersCycled;
-    }
-
-    const monomersAll: string[][] = [];
-
-    const resHwe = helmHelper.createHelmWebEditor();
-    const resMol = resHwe.editor.m;
-
-    let counter = 0;
-    const p = new JSDraw2.Point(0, 0);
-    for (let i = 0; i < monomers.length; i++) {
-      const linkedPositions = this.getLinkedPositions(monomers[i], rules.reactionRules);
-      const [monomersCycled, allPos1, allPos2, ruleN] =
-        this.getAllReactants(rules.reactionRules, monomers[i], linkedPositions);
-
-      if (allPos1.length >= 1) {
-        const ch1 = new Array<string>(allPos2[0] - 1);
-        const ch2 = new Array<string>(monomersCycled.length - allPos2[0]);
-        for (let j = 0; j < allPos2[0] - 1; j++) {
-          const elem = ch1[j] = monomersCycled[j];
-          const bio: PtBio = {type: HelmTypes.AA, i: i, j: j, continuousId: counter};
-          const atom: PtAtom = new JSDraw2.Atom<HelmType, PtBio>(p, elem, bio);
-          resMol.addAtom(atom);
-
-          if (j > 0) {
-            const atom1 = resMol.atoms[counter - 1];
-            const atom2 = resMol.atoms[counter];
-            const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-            bond.r1 = 2;
-            bond.r2 = 1;
-            resMol.addBond(bond);
-          }
-          counter++;
-        }
-
-        for (let j = allPos2[0]; j < monomersCycled.length; j++) {
-          const elem = ch2[j - allPos2[0]] = monomersCycled[j];
-          const bio: PtBio = {type: HelmTypes.AA, i: i, j: j, continuousId: counter};
-          const atom: PtAtom = new JSDraw2.Atom<HelmType, PtBio>(p, elem, bio);
-          resMol.addAtom(atom);
-
-          if (j > allPos2[0]) {
-            const atom1 = resMol.atoms[counter - 1];
-            const atom2 = resMol.atoms[counter];
-            const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-            bond.r1 = 2;
-            bond.r2 = 1;
-            resMol.addBond(bond);
-          }
-          counter++;
-        }
-
-        resMol.atoms[allPos1[0] - 1].elem = ch1[allPos1[0] - 1] = rules.reactionRules[ruleN[0]].name;
-
-        for (let j = 0; j < linkages.length; j++) {
-          if (linkages[j].fMonomer > allPos2[0]) {
-            linkages[j].fMonomer -= allPos2[0];
-            linkages[j].fChain++;
-          }
-          if (linkages[j].sMonomer > allPos2[0]) {
-            linkages[j].sMonomer -= allPos2[0];
-            linkages[j].sChain++;
-          }
-        }
-        linkages.push({
-          fChain: 0,
-          sChain: 0,
-          fMonomer: allPos1[0],
-          sMonomer: allPos2[0] - 1,
-          fR: 3,
-          sR: 2,
-        });
-
-        linkages.push({
-          fChain: 0,
-          sChain: 1,
-          fMonomer: allPos1[0],
-          sMonomer: 1,
-          fR: 4,
-          sR: 1,
-        });
-
-        const monomersReady1 = new Array<string>(ch1.length);
-        for (let j = 0; j < ch1.length; j++)
-          monomersReady1[j] = `[${ch1[j]}]`;
-        const monomersReady2 = new Array<string>(ch2.length);
-        for (let j = 0; j < ch2.length; j++)
-          monomersReady2[j] = `[${ch2[j]}]`;
-
-        monomersAll.push(ch1);
-        monomersAll.push(ch2);
-      } else {
-        for (let j = 0; j < monomers[i].length; j++) {
-          const elem = monomers[i][j];
-          const bio: PtBio = {type: HelmTypes.AA, i: i, j: j, continuousId: counter};
-          const atom: PtAtom = new JSDraw2.Atom<HelmType, PtBio>(p, elem, bio);
-          resMol.addAtom(atom);
-
-          if (j > 0) {
-            const atom1 = resMol.atoms[counter - 1];
-            const atom2 = resMol.atoms[counter];
-            const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-            bond.r1 = 2;
-            bond.r2 = 1;
-            resMol.addBond(bond);
-          }
-          counter++;
-        }
-        monomersAll.push(monomers[i]);
-      }
-    }
-
-    for (const l of linkages) {
-      const atom1 = resMol.atoms[l.fMonomer - 1];
-      const atom2 = resMol.atoms[l.sMonomer - 1];
-      const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-      bond.r1 = l.fR;
-      bond.r2 = l.sR;
-      resMol.addBond(bond);
-    }
-
-    const chain = new Chain(monomersAll, linkages, resMol, helmHelper);
+  /** Parse from separator or sequence notation (template)  */
+  static fromSeparator(sequence: string, helmHelper: IHelmHelper): Chain {
+    const [linkages, mainFragments] = parseSeparator(sequence);
+    const chain = new Chain(mainFragments, linkages, helmHelper);
     return chain;
   }
 
-  /** Parse harmonized sequence notation (template)  */
-  static parseNotation(sequence: string, helmHelper: IHelmHelper): Chain {
-    const mainFragments: string[][] = [];
-
-    const linkages: Linkage[] = [];
-
-    const resHwe = helmHelper.createHelmWebEditor();
-    const resMol = resHwe.editor.m;
-
-    const rxp = /(\(.\d+\))?\{[^\}]*\}/g;
-    const seqs: string [] = [];
-    seqs.push(sequence.replaceAll(rxp, ''));
-
-    //const l = (rxpRes?.length) ?? -1;
-
-    const matches = sequence.matchAll(rxp);
-    //const rxpRes = rxp.exec(sequence);
-    for (const m of matches) {
-      const str = m![0];
-      if (str)
-        seqs.push(str);
-    }
-
-    let counter = 0;
-    for (let i = 0; i < seqs.length; i++) {
-      const splMonomers = seqs[i].split('-');
-      const monomers: string [] = new Array<string>(splMonomers.length);
-      let spmCount: number = 0;
-      for (let j = 0; j < splMonomers.length; j++) {
-        const monomer = splMonomers[j].replace('{', '').replace('}', '');
-        if (monomer !== '') {
-          monomers[j] = monomer;
-          counter++;
-          spmCount++;
-        } else {
-          linkages.push({fChain: i, sChain: i + 1, fMonomer: counter, sMonomer: counter + 1, fR: 1, sR: 1});
-        }
-      }
-      mainFragments.push(monomers.slice(0, spmCount));
-    }
-
-    counter = 0;
-    const p = new JSDraw2.Point(0, 0);
-    for (let i = 0; i < mainFragments.length; i++) {
-      for (let j = 0; j < mainFragments[i].length; j++) {
-        if (!!mainFragments[i][j]) {
-          const elem = mainFragments[i][j];
-          const bio: PtBio = {type: HelmTypes.AA, i: i, j: j, continuousId: counter};
-          const atom = new JSDraw2.Atom<HelmType, IHelmBio>(p, elem, bio);
-          resMol.addAtom(atom);
-
-          if (j !== 0) {
-            const atom1 = resMol.atoms[counter - 1];
-            const atom2 = resMol.atoms[counter];
-            const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-            bond.r1 = 2;
-            bond.r2 = 1;
-            resMol.addBond(bond);
-          }
-
-          counter++;
-          p.x += JSDraw2.Editor.BONDLENGTH; // Inspired by HELMWebEditor
-        }
-        p.y += 4 * JSDraw2.Editor.BONDLENGTH; // Inspired by HELMWebEditor
-      }
-    }
-
-    for (let i = 0; i < linkages.length; i++) {
-      const atom1 = resMol.atoms[linkages[i].fMonomer - 1];
-      const atom2 = resMol.atoms[linkages[i].sMonomer - 1];
-      const bond = new JSDraw2.Bond<HelmType, IHelmBio>(atom1, atom2);
-      bond.r1 = linkages[i].fR;
-      bond.r2 = linkages[i].sR;
-      resMol.addBond(bond);
-    }
-
-    const chain = new Chain(mainFragments, linkages, resMol, helmHelper);
+  /** Parse harmonized sequence (template) from pseudo helm */
+  static fromHelm(sequence: string, helmHelper: IHelmHelper) : Chain {
+    const [linkages, mainFragments] = parseHelm(sequence);
+    const chain = new Chain(mainFragments, linkages, helmHelper);
     return chain;
   }
 
-  getHelmChanged(changeNumber: number, monomer: string): string {
-    //TODO: make more efficient
-    let counter = 0;
-    let idx1 = 0;
-    let idx2 = 0;
-    loop1:
-    for (let i = 0; i < this.monomers.length; i++) {
-      loop2:
-      for (let j = 0; j < this.monomers[i].length; j++) {
-        if (counter == changeNumber) {
-          idx1 = i;
-          idx2 = j;
-          break loop1;
-        }
-        counter++;
-      }
-    }
-
-    const previous = this.monomers[idx1][idx2];
-
-    this.monomers[idx1][idx2] = `[${monomer}]`;
-    const res = this.getHelm();
-    this.monomers[idx1][idx2] = previous;
-
-    return res;
-  }
-
-  /** Gets harmonized sequence (template) pseudo helm */
-  getNotationHelm(): string {
-    return this.getHelm();
-  }
-
-  /** Gets harmonized sequence (template) pseudo helm */
-  getHelm(): string {
-    let helm = '';
-    for (let i = 0; i < this.monomers.length; i++) {
-      if (i > 0)
-        helm += '|';
-
-      helm += `PEPTIDE${i + 1}{`;
-
-      for (let j = 0; j < this.monomers[i].length; j++) {
-        if (j > 0)
-          helm += '.';
-        const symbol = this.monomers[i][j];
-        helm += symbol.length > 1 ? `[${symbol}]` : symbol;
-      }
-      helm += `}`;
-    }
-
-    helm += '$';
-
-    for (let i = 0; i < this.linkages.length; i++) {
-      if (i > 0)
-        helm += '|';
-      helm += `PEPTIDE${this.linkages[i].fChain + 1},PEPTIDE${this.linkages[i].sChain + 1},`;
-
-      helm += `${getInnerIdx(this.linkages[i].fMonomer - 1, this.monomers)[0] + 1}:R${this.linkages[i].fR}-`;
-      helm += `${getInnerIdx(this.linkages[i].sMonomer - 1, this.monomers)[0] + 1}:R${this.linkages[i].sR}`;
-    }
-
-    helm += '$$$' + 'V2.0';
-    return helm;
-  }
-
   getNotation(): string {
-    const atoms = this.mol.atoms;
-    const bonds = this.mol.bonds;
-    const chains: number[] = [];
-    const specialBonds: number[] = [];
-    for (let i = 0; i < bonds.length!; i++) {
-      //@ts-ignore
-      if (bonds[i].a1.bio.i !== bonds[i].a2.bio.i)
-        specialBonds.push(i);
-    }
-
-    for (let i = 0; i < atoms.length!; i++) {
-      //@ts-ignore
-      const atomChain = atoms[i].bio?.i;
-      if (atomChain + 1 > chains.length)
-        chains.push(1);
-      else
-        chains[atomChain]++;
-    }
-
-    const simpleChains: string[][] = new Array(chains.length);
-    let counter = 0;
-    for (let i = 0; i < chains.length!; i++) {
-      const simpleChain: string[] = new Array(chains[i]);
-      for (let j = 0; j < chains[i]; j++) {
-        simpleChain[j] = atoms[counter].elem;
-        counter++;
-      }
-
-      simpleChains[i] = simpleChain;
-    }
-
-    let res = '';
-    for (let i = 0; i < simpleChains.length; i++) {
-      let chainAdd = '';
-
-      for (let j = 0; j < simpleChains[i].length; j++)
-        chainAdd += `${j == 0 ? '' : '-'}${simpleChains[i][j]}`;
-
-      if (i !== 0) {
-        const rxp = /(\(.\d+\))/;
-        const match = chainAdd.match(rxp);
-        chainAdd = chainAdd.replace(match?.[0]!, '');
-        const group = match ? match?.[0]! : '';
-        chainAdd = `${group}{${chainAdd}}`;
-      } else {
-        if (simpleChains.length > 1) {
-          //@ts-ignore
-          const firstAtomLinks = bonds[specialBonds[0]].a1.bio.i == 0 && bonds[specialBonds[0]].a1.bio.j == 0;
-          //@ts-ignore
-          const secondAtomLinks = bonds[specialBonds[0]].a2.bio.i == 1 && bonds[specialBonds[0]].a1.bio.j == 0;
-          if (firstAtomLinks && secondAtomLinks)
-            chainAdd += '-';
-        }
-      }
-
-      res += chainAdd;
-    }
-
-    return res;
+    return helmMolToNotation(this.mol);
   }
 
-  protected static getLinkedPositions(monomers: string[], rules: RuleLink[] | RuleReaction []):
-    [number, number, number][] {
-    const result: [number, number, number][] = [];
-
-    for (let i = 0; i < rules.length; i++) {
-      let firstFound = false;
-      let secondFound = false;
-      let firstIsFirst = false;
-      let firstEntryIndex = -1;
-      let secondEntryIndex = -1;
-      const add = `(${rules[i].code})`;
-
-      const [firstMonomers, secondMonomers] = getMonomerPairs(rules[i]);
-
-      if (firstMonomers.length > 0) {
-        for (let j = 0; j < firstMonomers.length; j++) {
-          for (let k = 0; k < monomers.length; k++) {
-            if (monomers[k].includes(add)) {
-              if (firstFound) {
-                if (firstIsFirst && monomers[k] == secondMonomers[j] + add) {
-                  secondFound = true;
-                  secondEntryIndex = k;
-                  break;
-                } else if (!firstIsFirst && monomers[k] == firstMonomers[j] + add) {
-                  secondFound = true;
-                  secondEntryIndex = k;
-                  break;
-                } else {
-                  continue;
-                }
-              } else {
-                if (monomers[k] == firstMonomers[j] + add) {
-                  firstFound = true;
-                  firstIsFirst = true;
-                  firstEntryIndex = k;
-                } else if (monomers[k] == secondMonomers[j] + add) {
-                  firstFound = true;
-                  firstIsFirst = false;
-                  firstEntryIndex = k;
-                } else {
-                  continue;
-                }
-              }
-            }
-          }
-
-          if (!(firstFound && secondFound))
-            continue;
-          else if (firstIsFirst)
-            result.push([firstEntryIndex, secondEntryIndex, i]);
-          else
-            result.push([secondEntryIndex, firstEntryIndex, i]);
-        }
-      } else {
-        for (let k = 0; k < monomers.length; k++) {
-          if (monomers[k].includes(add)) {
-            if (firstFound) {
-              if (firstIsFirst && monomers[k]) {
-                secondFound = true;
-                secondEntryIndex = k;
-                break;
-              } else if (!firstIsFirst && monomers[k]) {
-                secondFound = true;
-                secondEntryIndex = k;
-                break;
-              } else {
-                continue;
-              }
-            } else {
-              firstFound = true;
-              firstIsFirst = true;
-              firstEntryIndex = k;
-            }
-          }
-        }
-
-        if (!(firstFound && secondFound))
-          continue;
-        else if (firstIsFirst)
-          result.push([firstEntryIndex, secondEntryIndex, i]);
-        else
-          result.push([secondEntryIndex, firstEntryIndex, i]);
-      }
-    }
-
-    return result;
-  }
-
-  protected static getAllCycles(rules: RuleLink[], monomers: string [], positions: [number, number, number][]):
-    [string [], number [], number [], number [], number []] {
-    const allPos1: number [] = [];
-    const allPos2: number [] = [];
-    const allAttaches1: number [] = [];
-    const allAttaches2: number [] = [];
-    const count = positions.length;
-
-    for (let i = 0; i < count; i++) {
-      if (positions[i][0] == -1)
-        continue;
-
-      const ruleNum = positions [i][2];
-      const code = rules[ruleNum].code;
-
-      monomers[positions[i][0]] = monomers[positions[i][0]].replace(`(${code})`, '');
-      monomers[positions[i][1]] = monomers[positions[i][1]].replace(`(${code})`, '');
-
-      allPos1.push(positions[i][0] + 1);
-      allPos2.push(positions[i][1] + 1);
-      allAttaches1.push(rules[ruleNum].firstLinkingGroup);
-      allAttaches2.push(rules[ruleNum].secondLinkingGroup);
-    }
-
-    return [monomers, allPos1, allPos2, allAttaches1, allAttaches2];
+  getHelm(): string {
+    if (this.underRules)
+      return fromObjectsToHelm(this.linkagesUnderRules, this.monomersUnderRules);
+    else
+      return fromObjectsToHelm(this.linkages, this.monomers);
   }
 
-  protected static getAllReactants(rules: RuleReaction[], monomers: string [], positions: [number, number, number][]):
-    [string [], number [], number [], number []] {
-    const allPos1: number [] = [];
-    const allPos2: number [] = [];
-    const rule: number [] = [];
-    const count = positions.length;
-
-    for (let i = 0; i < count; i++) {
-      if (positions[i][0] == -1)
-        continue;
-
-      const ruleNum = positions [i][2];
-      const code = rules[ruleNum].code;
-      monomers[positions[i][0]] = monomers[positions[i][0]].replace(`(${code})`, '');
-      monomers[positions[i][1]] = monomers[positions[i][1]].replace(`(${code})`, '');
+  /** Get macromolecule from harmonized sequence (template) */
+  applyRules(rules: Rules): void {
+    const sequence = this.getNotation();
 
-      allPos1.push(positions[i][0] + 1);
-      allPos2.push(positions[i][1] + 1);
-      rule.push(positions[i][2]);
-    }
+    const [linkages, mainFragments] = handleDuplicated(sequence, rules);
+    const monomers = new Array<Array<string>>(mainFragments.length);
+    handleLinkRules(mainFragments, monomers, linkages, rules);
+    handleReactionRules(monomers, linkages, rules);
 
-    return [monomers, allPos1, allPos2, rule];
+    this.underRules = true;
+    this.linkagesUnderRules = linkages;
+    this.monomersUnderRules = monomers;
+    this.molUnderRules = getHelmMol(linkages, monomers, this.helmHelper);
   }
 
   public check(throwError: boolean = false): string[] {