Biomolecular Computers

What are biomolecules?

What is a Computer? compū´ter n. …; automatic electronic apparatus for making calculations or controlling operations that are expressible in numerical or logical terms;… The Concise Oxford Dictionary

What is a Computer? compū´ter n. …; automatic electronic apparatus for making calculations or controlling operations that are expressible in numerical or logical terms;… The Concise Oxford Dictionary

What is a Computer? → Much of molecular biology compū´ter n. …; automatic electronic apparatus for making calculations or controlling operations that are expressible in numerical or logical terms;… → Much of molecular biology

Molecular machines in operation RNA Polymerase transcribes DNA to RNA Ribosomes translate RNA to Proteins

Computing automata in operation RNA Polymerase transcribes DNA to RNA Ribosomes translate RNA to Proteins Both can be viewed as finite state transducers

Review of published research Mechanical Turing machine (DNA 5, MIT, 1999) Programmable and autonomous molecular computing machine (Nature, 2002) DNA molecule provides computing machine with both data and fuel (PNAS 2003)

Review of published research Mechanical Turing machine (DNA 5, MIT, 1999) Programmable and autonomous molecular computing machine (Nature, 2002) DNA molecule provides computing machine with both data and fuel (PNAS 2003)

A mechanical Turing machine

A 4 3 5 2 1

Software molecules

“Software” “molecules”

Control via recognition-based conformational change

Medicine in 2020: “Doctor in a Cell” Programmable Computer Molecular Output Molecular Input Programmable Computer

Medicine in 2050: “Doctor in a Cell” Programmable Computer Molecular Input Molecular Output

A 2-state, 2-symbol finite automaton

Review of published research Mechanical Turing machine (DNA 5, MIT, 1999) Programmable and autonomous molecular computing machine (Nature, 2002) DNA molecule provides computing machine with both data and fuel (PNAS 2003)

The molecular automaton

Additional 2-state, 2-symbol automata

Software molecules

Running different molecular programs

Software breakpoints

Automaton performance 1012 automata run independently and in parallel on potentially distinct inputs in 120 µl at room temperature at combined rate of 109 transitions per second with accuracy ≥ 99.8% per transition, consuming less than 10-9 Watt.

Checking all molecules to be essential

Checking all molecules to be essential: Why bother? Half the hardware (only one enzyme) Ligase only ATP consuming components. So no energy?

Information Destruction in Electronic Computers Via erasure: Resetting bits to zero Thermodynamically uphill since decreases entropy

Information Destruction in Biology Happens all the time through biopolymer cleavage and digestion Thermodynamically downhill: Increases entropy AND dissipates heat Our discovery: Can be used to compute without additional energy

DNA molecule as computer fuel

Automaton performance 3x1012 automata/µl (240x) Performing 6.6x1010 transitions/sec/µl (8000x) [New performance measure?] With transition fidelity of 99.9% (2x) Dissipating 10-8 W/µl as heat at ambient temperature

Review of published research Mechanical Turing machine (DNA 5, MIT, 1999) Programmable and autonomous molecular computing machine (Nature, 2002) DNA molecule provides computing machine with both data and fuel (PNAS 2003)

התקן החישוב הביולוגי הכי קטן צוות מדענים ממכון וייצמן למדע (ישראל) סיגלו מולקולות דנ"א שיפעלו כמחשבים מולקולריים זעירים (נאנו-מחשבים). מולקולות דנ"א הן הקלט, הפלט וה'תוכנה' ואנזים הפועל עליהן הוא ה'חומרה'. בניסויים נמצא כי מיקרו-ליטר אחד של תמיסת מלח, המכילה 3 טריליון התקני חישוב כאלה, מסוגל לבצע 66 מיליארד פעולות בשנייה. את האנרגיה לפעולות מספק הדנ"א עצמו כשאנזים ה'חומרה' פועל עליו. התוצאות הוכרזו ב24- בפברואר 2003 ברשומות האקדמיה הלאומית למדעים. צוות החוקרים: ד"ר רבקה אדר, יעקב בננסון, פרופ' צבי ליבנה, ד"ר תמר פז-אליצור, ופרופ' אהוד שפירא - כולם מישראל.

Current Research Diagnostic/therapeutic molecular automaton

Medicine in 2050: “Doctor in a Cell” Programmable Computer Output molecules Input molecules Programmable Computer

Research in 2005: “Doctor in a test tube” Output molecules : Drug molecules Input molecules: Disease markers Programmable Computer: Diagnostic/therapeutic automaton

The students (and friends)

Karl Popper’s Three-worlds Ontology World III: Objective Mathematical and linguistic entities, words, poems, articles, computer programs World II: Subjective Mental entities and processes, thoughts, dreams, decisions, feelings World I: Material Physical entities and processes, atoms, galaxies, artifacts, organisms

Computers in Popper’s Three-worlds Ontology World III: Objective Mathematical models of computation World II: Subjective ? World I: Material Physical [computer] systems

What is a Computer? compū´ter n. …; a physical system that is a realization of a mathematical model of computation; … No such computers. A faulty computer? (Intel FP bug) The operation of the physical system needs to be interpreted as, and trusted to be, a computation.

What is a Computer? compū´ter n. …; a physical system deemed to be a realization of a mathematical model of computation; …

What is a Computer? compū´ter n. …; a physical system deemed to be a realization of a mathematical model of computation; … All three worlds are needed for this definition.

Computers in Popper’s Three-worlds Ontology Mathematical model of computation Deemed, interpreted, and trusted to be Physical system