Saturday, August 02, 2025

Demis Hassabis

 demis-hassabis-2-transcript

"with the Alpha X projects, so I’m thinking AlphaGo, of course, AlphaFold, what they really are is we are building models of very combinatorially, high dimensional spaces that if you try to brute force a solution, find the best move and go, or find the exact shape of a protein, and if you enumerated all the possibilities, there wouldn’t be enough time in the time of the universe."

You're absolutely right — both AlphaGo and AlphaFold tackled combinatorially explosive problems where brute-force enumeration is impossible. What made the Alpha projects successful is not just computational power, but smart modeling of massive search spaces. Here's how they approached it:


🧠 The Core Idea: Model the Space, Don't Enumerate It

Both problems involve astronomical possibilities:

ProblemSize of Search Space
Go>10¹⁷⁰ possible board configurations
Protein folding~10³⁰⁰ possible conformations for a small protein

Searching these spaces directly is like trying to find a needle in a universe of haystacks. So they didn't search directly — they learned patterns that make intelligent guesses far more efficient than brute force.


🔍 How AlphaGo Did It (Game Playing)

AlphaGo used:

  1. Policy network – predicts the most promising next moves (reducing branching factor).

  2. Value network – estimates who is winning from any given board state.

  3. Monte Carlo Tree Search (MCTS) – selectively explores move sequences using the above networks to prioritize paths.

Key Insight: Don’t simulate every move — simulate only the most relevant ones using learned heuristics.


🧬 How AlphaFold Did It (Protein Folding)

AlphaFold (especially AlphaFold 2) used:

  1. Large-scale training on protein databases – learned statistical patterns in protein sequences and structures.

  2. Evoformer – a deep neural architecture that infers pairwise relationships between amino acids.

  3. Structure module – predicts 3D structure from inferred relationships.

Key Insight: It’s not necessary to simulate every quantum force or physical interaction — statistical modeling of evolutionary patterns is enough to approximate structure.


🎯 Common Themes: How They Conquered the Impossible

FeatureAlphaGoAlphaFold
Problem TypePlanning / OptimizationStructural Prediction
StrategyGuided simulation (MCTS + NN)Learned statistical approximation
Brute-force FeasibilityImpossibleImpossible
Key InnovationDeep learning + Tree searchTransformer-based structure prediction
Use of Domain KnowledgeYes (rules of Go, board symmetry)Yes (biology, multiple sequence alignment)

🧠 Deep Learning as a Shortcut Through Combinatorics

Rather than "solve" the entire space, they learned from data how to:

  • Recognize patterns that compress the space.

  • Prioritize plausible solutions (moves or folds).

  • Generalize from past data without needing full enumeration.

This is exactly why brute force is out, and learning is in — deep models are function approximators that give you good answers fast.


Would you like a deeper dive into AlphaFold 2’s architecture, or a visual analogy of how these spaces are compressed through learning?

You said:
sure
ChatGPT said:

Great! Let's break this down with two things:

  1. A visual analogy to understand how deep learning compresses huge spaces.

  2. A simplified architecture breakdown of AlphaFold 2, since it's a pinnacle of this idea.


🧠 1. Visual Analogy: How Deep Models Shortcut Massive Search Spaces

Imagine you're dropped into a dark mountain range the size of a planet. You're told to find the highest peak — but you can't see more than a few feet around you, and there's no map.

👎 Brute Force:

  • You try every path up every hill.

  • You’d die of old age before covering 0.000000001% of the area.

👍 Deep Learning Strategy (like AlphaGo or AlphaFold):

  • Before you even start, you’re trained on thousands of aerial photos of mountain ranges.

  • You learn to spot subtle signs of elevation changes.

  • When dropped into a new mountain range, you instantly guess the best few paths to try first — and you’re right 95% of the time.

Deep learning doesn’t "solve" the space — it learns a compressed representation of it, guided by experience.

This is how AlphaFold can predict a protein’s shape without evaluating all 10³⁰⁰ possibilities — it’s been "shown enough mountain ranges" (i.e., protein families and structures) to generalize well.


🧬 2. Simplified View of AlphaFold 2 Architecture

AlphaFold 2 is like a three-step system:

🧩 Step 1: Multiple Sequence Alignment (MSA)

  • Aligns your input protein sequence with related sequences from evolution (across species).

  • This gives clues about which amino acids evolve together, implying they might be close in 3D space.

Imagine tracing the ancestry of words across languages to infer grammar rules — that’s what MSA is doing with proteins.


🔁 Step 2: Evoformer

  • A Transformer-based neural network (like what powers GPT, but specialized).

  • It passes information back and forth between:

    • MSA features

    • Pairwise residue relationships (a 2D map of how likely two amino acids are to be near each other)

  • Think of this as massive relational reasoning: figuring out if A is near B, and B is near C, then what’s A’s relation to C?

It’s like a very smart Sudoku solver — piecing together spatial relationships between parts.


🧱 Step 3: Structure Module

  • Takes that 2D map and predicts the 3D atomic coordinates of the protein.

  • Uses a differentiable 3D geometry model — it knows how to build shapes from angles and distances.

Like going from a 2D floor plan to a full 3D house model.


🧠 What Makes AlphaFold 2 So Powerful?

  • It models structure and sequence jointly, not separately.

  • It iteratively refines predictions — feeding output structure back into the model to improve it.

  • Trained on a massive protein structure database (PDB) + evolutionary data.


TL;DR – Alpha Projects’ Superpower:

They didn’t brute-force the universe. They learned to see the shortcuts.

  • AlphaGo: Learns which moves matter in a vast game space.

  • AlphaFold: Learns which patterns in sequences matter for folding.

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