@aleph-ai/tinyaleph 1.2.1 → 1.3.0

package/backends/bioinformatics/folding.js

@@ -0,0 +1,454 @@
+/**
+ * Protein Folding via Kuramoto Oscillator Dynamics
+ * 
+ * Models protein folding as entropy minimization through coupled oscillator synchronization.
+ * Each amino acid residue is an oscillator with:
+ * - Natural frequency derived from its prime value
+ * - Coupling strength from contact propensity (hydrophobic, electrostatic, resonance)
+ * 
+ * Folded state = synchronized oscillators = low entropy configuration
+ */
+
+const { AMINO_ACID_PRIMES, AMINO_ACID_PROPERTIES, getChargeFromPrime, getHydrophobicityFromPrime } = require('./encoding');
+
+// Import physics modules - with fallback for standalone testing
+let KuramotoModel, NetworkKuramoto, AdaptiveKuramoto, shannonEntropy, primeToFrequency, calculateResonance;
+
+try {
+  const physics = require('../../physics');
+  const core = require('../../core');
+  
+  KuramotoModel = physics.KuramotoModel;
+  NetworkKuramoto = physics.NetworkKuramoto || physics.KuramotoModel;
+  AdaptiveKuramoto = physics.AdaptiveKuramoto || physics.KuramotoModel;
+  shannonEntropy = physics.shannonEntropy;
+  primeToFrequency = core.primeToFrequency;
+  calculateResonance = core.calculateResonance;
+} catch (e) {
+  // Fallback implementations for standalone testing
+  primeToFrequency = (p, base = 1, logScale = 10) => base + Math.log(p) / logScale;
+  calculateResonance = (p1, p2) => {
+    const ratio = Math.max(p1, p2) / Math.min(p1, p2);
+    const PHI = 1.618033988749895;
+    return 1 / (1 + Math.abs(ratio - PHI));
+  };
+  shannonEntropy = (probs) => {
+    let H = 0;
+    for (const p of probs) {
+      if (p > 1e-10) H -= p * Math.log2(p);
+    }
+    return H;
+  };
+}
+
+/**
+ * FoldingTransform
+ * 
+ * Protein folding modeled as entropy minimization via Kuramoto synchronization.
+ */
+class FoldingTransform {
+  constructor(options = {}) {
+    this.options = {
+      coupling: options.coupling || 0.3,
+      temperature: options.temperature || 1.0,
+      maxSteps: options.maxSteps || 1000,
+      dt: options.dt || 0.01,
+      convergenceThreshold: options.convergenceThreshold || 0.95,
+      minSequenceSeparation: options.minSequenceSeparation || 4,
+      hydrophobicWeight: options.hydrophobicWeight || 0.4,
+      electrostaticWeight: options.electrostaticWeight || 0.3,
+      resonanceWeight: options.resonanceWeight || 0.3,
+      ...options
+    };
+  }
+  
+  /**
+   * Fold protein using Kuramoto oscillator dynamics
+   * @param {number[]} proteinPrimes - Protein sequence as amino acid primes
+   * @returns {object} Folding result with structure information
+   */
+  fold(proteinPrimes) {
+    const n = proteinPrimes.length;
+    
+    if (n < 4) {
+      return {
+        success: false,
+        error: 'Protein too short for folding simulation',
+        length: n
+      };
+    }
+    
+    // Initialize oscillators with frequencies from primes
+    const frequencies = proteinPrimes.map(p => primeToFrequency(p, 1, 10));
+    
+    // Build contact propensity matrix
+    const contactMatrix = this.computeContactPropensity(proteinPrimes);
+    
+    // Initialize phases randomly
+    const phases = new Array(n).fill(0).map(() => Math.random() * 2 * Math.PI);
+    
+    // Evolution tracking
+    const history = {
+      orderParameter: [],
+      entropy: [],
+      energyLandscape: []
+    };
+    
+    // Kuramoto evolution
+    let order = 0;
+    let step = 0;
+    
+    for (step = 0; step < this.options.maxSteps; step++) {
+      // Compute phase updates (Kuramoto equation)
+      const dPhases = this.kuramotoStep(phases, frequencies, contactMatrix);
+      
+      // Apply thermal noise
+      for (let i = 0; i < n; i++) {
+        phases[i] += dPhases[i] * this.options.dt;
+        phases[i] += this.thermalNoise() * Math.sqrt(this.options.dt);
+        // Keep phases in [0, 2π]
+        phases[i] = ((phases[i] % (2 * Math.PI)) + 2 * Math.PI) % (2 * Math.PI);
+      }
+      
+      // Calculate order parameter
+      order = this.calculateOrderParameter(phases);
+      const entropy = this.calculatePhasesEntropy(phases);
+      const energy = this.calculateFoldingEnergy(phases, proteinPrimes, contactMatrix);
+      
+      history.orderParameter.push(order);
+      history.entropy.push(entropy);
+      history.energyLandscape.push(energy);
+      
+      // Check convergence
+      if (order > this.options.convergenceThreshold) {
+        break;
+      }
+    }
+    
+    // Extract structure from final phases
+    const structure = this.phasesToStructure(phases, proteinPrimes);
+    const contacts = this.extractContacts(phases, this.options.minSequenceSeparation);
+    
+    return {
+      success: true,
+      phases: [...phases],
+      structure,
+      contacts,
+      orderParameter: order,
+      finalEntropy: history.entropy[history.entropy.length - 1],
+      foldingFreeEnergy: this.estimateFreeEnergy(order, proteinPrimes),
+      stepsToConverge: step,
+      history,
+      secondaryStructure: this.assignSecondaryStructure(structure),
+      compactness: this.calculateCompactness(contacts, n)
+    };
+  }
+  
+  /**
+   * Compute Kuramoto phase derivatives
+   */
+  kuramotoStep(phases, frequencies, coupling) {
+    const n = phases.length;
+    const dPhases = new Array(n).fill(0);
+    
+    for (let i = 0; i < n; i++) {
+      // Natural frequency term
+      dPhases[i] = frequencies[i];
+      
+      // Coupling term (sum over all connected oscillators)
+      for (let j = 0; j < n; j++) {
+        if (i !== j && coupling[i][j] > 0) {
+          dPhases[i] += coupling[i][j] * Math.sin(phases[j] - phases[i]);
+        }
+      }
+    }
+    
+    return dPhases;
+  }
+  
+  /**
+   * Compute contact propensity matrix from amino acid properties
+   */
+  computeContactPropensity(proteinPrimes) {
+    const n = proteinPrimes.length;
+    const matrix = Array(n).fill(null).map(() => Array(n).fill(0));
+    
+    for (let i = 0; i < n; i++) {
+      for (let j = i + this.options.minSequenceSeparation; j < n; j++) {
+        const pi = proteinPrimes[i];
+        const pj = proteinPrimes[j];
+        
+        // Resonance component (golden ratio proximity)
+        const resonance = calculateResonance(pi, pj);
+        
+        // Hydrophobic interaction (smaller primes are more hydrophobic)
+        const hi = getHydrophobicityFromPrime(pi);
+        const hj = getHydrophobicityFromPrime(pj);
+        const hydrophobic = this.hydrophobicPotential(hi, hj);
+        
+        // Electrostatic interaction
+        const qi = getChargeFromPrime(pi);
+        const qj = getChargeFromPrime(pj);
+        const electrostatic = this.electrostaticPotential(qi, qj);
+        
+        // Combined contact propensity
+        const propensity = 
+          this.options.resonanceWeight * resonance +
+          this.options.hydrophobicWeight * hydrophobic +
+          this.options.electrostaticWeight * electrostatic;
+        
+        matrix[i][j] = matrix[j][i] = Math.max(0, propensity) * this.options.coupling;
+      }
+    }
+    
+    return matrix;
+  }
+  
+  /**
+   * Hydrophobic potential: like attracts like
+   */
+  hydrophobicPotential(h1, h2) {
+    // Both hydrophobic (positive h): attract
+    // Both hydrophilic (negative h): weak attract
+    // Mixed: repel
+    if (h1 > 0 && h2 > 0) {
+      return Math.sqrt(h1 * h2) / 4;
+    } else if (h1 < 0 && h2 < 0) {
+      return Math.sqrt(-h1 * -h2) / 8;
+    } else {
+      return -0.1;
+    }
+  }
+  
+  /**
+   * Electrostatic potential: opposites attract
+   */
+  electrostaticPotential(q1, q2) {
+    if (q1 * q2 < 0) {
+      return 0.5;  // Opposite charges attract
+    } else if (q1 * q2 > 0) {
+      return -0.3;  // Same charges repel
+    }
+    return 0;
+  }
+  
+  /**
+   * Generate thermal noise
+   */
+  thermalNoise() {
+    // Box-Muller transform for Gaussian noise
+    const u1 = Math.random();
+    const u2 = Math.random();
+    const gaussian = Math.sqrt(-2 * Math.log(u1)) * Math.cos(2 * Math.PI * u2);
+    return gaussian * Math.sqrt(this.options.temperature) * 0.1;
+  }
+  
+  /**
+   * Calculate Kuramoto order parameter
+   */
+  calculateOrderParameter(phases) {
+    const n = phases.length;
+    let sumCos = 0, sumSin = 0;
+    
+    for (const phase of phases) {
+      sumCos += Math.cos(phase);
+      sumSin += Math.sin(phase);
+    }
+    
+    return Math.sqrt(sumCos * sumCos + sumSin * sumSin) / n;
+  }
+  
+  /**
+   * Calculate entropy of phase distribution
+   */
+  calculatePhasesEntropy(phases) {
+    const bins = 36;  // 10-degree bins
+    const histogram = Array(bins).fill(0);
+    
+    for (const phase of phases) {
+      const bin = Math.floor(phase / (2 * Math.PI) * bins);
+      histogram[Math.min(bin, bins - 1)]++;
+    }
+    
+    const probs = histogram.map(h => h / phases.length);
+    return shannonEntropy(probs);
+  }
+  
+  /**
+   * Calculate folding energy from phases and contacts
+   */
+  calculateFoldingEnergy(phases, primes, contactMatrix) {
+    let energy = 0;
+    const n = phases.length;
+    
+    for (let i = 0; i < n; i++) {
+      for (let j = i + this.options.minSequenceSeparation; j < n; j++) {
+        const phaseDiff = Math.abs(phases[i] - phases[j]);
+        const inContact = phaseDiff < 0.5 || phaseDiff > 2 * Math.PI - 0.5;
+        
+        if (inContact && contactMatrix[i][j] > 0) {
+          // Favorable contact
+          energy -= contactMatrix[i][j];
+        }
+      }
+    }
+    
+    return energy;
+  }
+  
+  /**
+   * Convert phases to structural information
+   */
+  phasesToStructure(phases, primes) {
+    const structure = [];
+    
+    for (let i = 0; i < phases.length; i++) {
+      // Phase determines backbone angles (phi, psi approximation)
+      const phi = (phases[i] - Math.PI) * 180 / Math.PI;
+      const nextPhase = phases[(i + 1) % phases.length];
+      const psi = (nextPhase - phases[i]) * 180 / Math.PI;
+      
+      structure.push({
+        residue: i,
+        prime: primes[i],
+        phase: phases[i],
+        phi,
+        psi,
+        secondaryStructure: this.classifySecondaryStructure(phi, psi)
+      });
+    }
+    
+    return structure;
+  }
+  
+  /**
+   * Classify secondary structure from backbone angles
+   */
+  classifySecondaryStructure(phi, psi) {
+    // Alpha helix: phi ≈ -60, psi ≈ -45
+    if (phi > -100 && phi < -30 && psi > -70 && psi < 0) {
+      return 'H';  // Helix
+    }
+    
+    // Beta sheet: phi ≈ -120, psi ≈ +120
+    if (phi > -180 && phi < -60 && (psi > 90 || psi < -90)) {
+      return 'E';  // Extended (sheet)
+    }
+    
+    // 3-10 helix: phi ≈ -49, psi ≈ -26
+    if (phi > -70 && phi < -30 && psi > -50 && psi < 0) {
+      return 'G';  // 3-10 helix
+    }
+    
+    return 'C';  // Coil
+  }
+  
+  /**
+   * Extract residue-residue contacts from phases
+   */
+  extractContacts(phases, minSeparation = 4, threshold = 0.5) {
+    const contacts = [];
+    const n = phases.length;
+    
+    for (let i = 0; i < n; i++) {
+      for (let j = i + minSeparation; j < n; j++) {
+        const phaseDiff = Math.abs(phases[i] - phases[j]);
+        const normalized = Math.min(phaseDiff, 2 * Math.PI - phaseDiff);
+        
+        if (normalized < threshold) {
+          contacts.push({
+            i,
+            j,
+            distance: normalized,
+            strength: 1 - normalized / threshold
+          });
+        }
+      }
+    }
+    
+    return contacts;
+  }
+  
+  /**
+   * Assign secondary structure elements
+   */
+  assignSecondaryStructure(structure) {
+    const ssSequence = structure.map(s => s.secondaryStructure).join('');
+    
+    // Find helices (runs of H)
+    const helices = [];
+    const helixPattern = /H{4,}/g;
+    let match;
+    while ((match = helixPattern.exec(ssSequence)) !== null) {
+      helices.push({ start: match.index, end: match.index + match[0].length - 1, type: 'helix' });
+    }
+    
+    // Find sheets (runs of E)
+    const sheets = [];
+    const sheetPattern = /E{3,}/g;
+    while ((match = sheetPattern.exec(ssSequence)) !== null) {
+      sheets.push({ start: match.index, end: match.index + match[0].length - 1, type: 'sheet' });
+    }
+    
+    return {
+      sequence: ssSequence,
+      helices,
+      sheets,
+      helixContent: (ssSequence.match(/H/g) || []).length / structure.length,
+      sheetContent: (ssSequence.match(/E/g) || []).length / structure.length
+    };
+  }
+  
+  /**
+   * Calculate compactness (contact order)
+   */
+  calculateCompactness(contacts, length) {
+    if (contacts.length === 0) return 0;
+    
+    const totalSeparation = contacts.reduce((sum, c) => sum + (c.j - c.i), 0);
+    return totalSeparation / (contacts.length * length);
+  }
+  
+  /**
+   * Estimate folding free energy
+   */
+  estimateFreeEnergy(orderParameter, primes) {
+    // ΔG ∝ -kT * ln(order parameter) - hydrophobic contribution
+    const kT = this.options.temperature;
+    const entropyTerm = -kT * Math.log(Math.max(orderParameter, 0.01));
+    
+    // Hydrophobic burial contribution
+    const hydrophobicPrimes = primes.filter(p => p <= 43);
+    const hydrophobicFraction = hydrophobicPrimes.length / primes.length;
+    const hydrophobicTerm = -hydrophobicFraction * 2.0;  // Favorable
+    
+    return entropyTerm + hydrophobicTerm;
+  }
+  
+  /**
+   * Simulated annealing for global minimum
+   */
+  anneal(proteinPrimes, options = {}) {
+    const startTemp = options.startTemp || 10.0;
+    const endTemp = options.endTemp || 0.1;
+    const coolingRate = options.coolingRate || 0.99;
+    
+    let temp = startTemp;
+    let bestResult = null;
+    
+    while (temp > endTemp) {
+      this.options.temperature = temp;
+      const result = this.fold(proteinPrimes);
+      
+      if (!bestResult || result.foldingFreeEnergy < bestResult.foldingFreeEnergy) {
+        bestResult = result;
+      }
+      
+      temp *= coolingRate;
+    }
+    
+    return bestResult;
+  }
+}
+
+module.exports = { FoldingTransform };