The Origins of Life: An Architectonic Perspective

Clarence E. Schutt Princeton University

28 March 2007

Dedicated to Max Perutz

(1914 - 2002)

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Outline of Today’s Presentation

1. Two Architectonic Principles from Schrödinger:

2. Order from order: Light, Crystals, Life

4. The Third Architectonic Principle: muscle contraction

-Negentropy

-The Aperiodic Crystal

3. Order from disorder: Proteins, Viruses

Schrödinger: “Is Life Based on the Laws of Physics?”

“What I wish to make clear … is …that from all that we have learnt about the structure of living matter, we must be prepared to find it working in a manner that cannot be reduced to the ordinary laws of physics. And that not on the ground that there is any ‘new force’ but …because the construction is different from anything we have yet tested in the physical laboratory.”

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Michael Polanyi: “Life’s Irreducible Structure (Science,1968)”

1891-1976

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“In this light the organism is shown to be, like a machine, a system which works according to two different principles: its structure serves as a boundary condition harnessing physical-chemical processes by which its organs perform their functions.”

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are needed to see this picture. The electric motor places constraints on the movement of the electrons

Two ideas from Schrödinger’s book, ‘What Is Life?’

The order in living systems on Earth is only in apparent violation of the second law of thermodynamics. Life feeds on ‘negative entropy’.

The stability of genes over the span of lifetimes suggests that they are aperiodic crystals, coding in their quantum states the plan of the organism.

ΔS universe ≥ 0

Max Perutz on ‘What Is Life?’

“The apparent contradictions between life and the statistical laws of physics can be resolved by invoking a science largely ignored by Schrödinger. That science is chemistry.”

ΔG life = ΔH life -TΔS life ≤ 0

“Given a source of free energy, a well-ordered configuration of atoms in a single molecule of an enzyme catalyst can direct the formation of an ordered stereospecific compound … thus creating order from disorder at the ultimate expense of solar energy.”

“Physics and the Riddle of Life”, Nature (326), 1987

Roger Penrose: The Entropy of Light

ΔSlight = Sinfrared - Sultraviolet ≥ 0

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At steady-state, the Earth radiates as much energy as it absorbs, but the radiated photons have greater degrees of freedom.

Proteins are ‘Polanyi Machines’

Living processes can be analyzed in terms of boundaries between distinctly different states of order. The elements of these ‘surfaces’ need not be connected.

The Sun-Earth ‘boundary’ is the set of all membranes containing photosynthetic proteins. One on side, free energy is in the form of photons, on the other it is contained in the chemical bonds of ATP.

Schutt & Lindberg, The New Architectonics: An Invitation to Structural Biology (2000)

H2O

H2 + ½ O2 + X

H2O(X) Activated substrate

2 H + O

MOH

OH

X

Energy Input

Chemical Pathways for Catalyzing Water Splitting

Solar >2500 0CTransition-state

Oxygenic Photosynthesis

Ferreira et al. (2004) Science

4 flas

hes

O2

evolves

Hypothesized mechanism:

PS-II - the ultimate Polanyi Machine

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Biomimetic water-oxidizing complex

Entropy or Enthalpy?Courtesy of Prof. Charles Dismukes, Princeton University

Max Perutz on ‘What Is Life?’

“I wonder why Schrödinger did not adhere to Delbrück’smuch better formulation of ‘a polymeric entity that arises by repetition of identical atomic structures’. One could argueover the distinction between aperiodic and identical, butDelbrück could not have meant structures that are completelycompletelyidentical, since these could contain no information.identical, since these could contain no information.””

“Physics and the Riddle of Life”, Nature (326), 1987

Protein cores are aperiodic crystals

Protein folding is driven by the entropy change of water

molecules (Kauzmann, 1959).

The hydrophobic cores of proteins are close-packed.(Richards, 1973).

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ΔSprotein = ΔSchain + ΔSwater ≥ 0

ras p21

Image created by Simon P. Brocklehurst

Max Perutz on ‘What is Life?’

“Chemists could also have told him that there is no problemin explaining stability of polymers that living matter is made of,because bond energies range from 3 eV upward, correspondingto a half-life of 1030 years at room temperature”

“The difficulty resides in explaining how their aperiodic patterns are accurately reproduced in each generation. There is no mention of this central problem in Schrödinger’s book”

“Physics and the Riddle of Life”, Nature (326), 1987

amino-acyl t-RNA synthetases are Polanyi Machines

Protein synthesis can be conceptualized as a ‘disordered’ pool of the 20 different amino acids separated by a boundary having ‘ordered’ linear sequences on the other side. It takes Gibbs free energy to ‘sort’ and assemble the amino acids into polypeptide chains.

Translation of the Genetic Code

Thermodynamics of Sorting

Protein synthesis is a disorder-to-order process. Amino-acyl t-RNA synthetases select amino acids from a

random pool.

υA / υB = [A]/[B] e -ΔGb/RT

ΔGb is the difference in binding energy of the side-chains, υA is the rate of charging t-RNA.

Protein Folding: The Second Code

The information contained within the one-dimensional amino acid sequence of a protein is

sufficient to dictate its three-dimensional structure.

Hn (p1, p2 …. pn) = ∑ pi log pi

“The Shannon entropy”

Schrödinger could not have anticipated that polymers could spontaneously undergo a disorder to order

process.

Strait & Dewey, ‘The Shannon Information Entropy of Protein Sequences’, Biophysical J. 71:148-155 (1996)

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TMV Self-Assembly: Disk to Helix

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D.L.D.CasparThe design of the whole is contained in the part.

Stuart Kauffmann: “The Adjacent Possible”

“In his famous book, What is Life?, Schrödinger asks ‘What is the source of the order in biology?’ He arrives at the idea … (of) a microcode carried in some sort of aperiodic crystal - which turned out to be DNA and RNA - so he is brilliantly right. But if you ask if got the essence of what makes something alive, it’s clear he didn’t.”

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Kauffmann concludes that to be ‘living’ an organism not only replicates, but must do work on its surroundings to explore new niches and create for itself new constraining structures (e.g. membranes).

www.edge.org

How do Polanyi machines perform reversible work?

ΔG life = reversible work life

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Protein machines doing work must control the (slow?) release of Gibbs free energy from ATP for maximum thermodynamic efficiency. Brownian motion must be kept to a minimum.

A.V. Hill: Energetics of Muscle Contraction

The astonishing thing about muscle is that the external load is transmitted directly to the energy producing molecules. It is akin to an electric motor where increasing the load results in more current in the coils (The Fenn Effect).

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Heat + work = K(Po - P)

Proc. Roy. Soc. B126, 136-195 (1938)1886-1977

‘Structure’ as Hierarchical Ordering

C.E. Schutt & U. Lindberg, “The New Architectonics: An

Invitation to Structural Biology”The Anatomical Record, 2000

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TensegritySculpture

Snelson Schutt and Lindberg

ActinFilament

Functional Unit of Muscle Contraction

The sarcomere is the basic unit of muscle structure. Actin filaments (rosa) move relative to myosin filaments (azul).

Central question: what drives the relative motion?

Huxley & Hansen (1954), Huxley & Neidegerke (1954)

Huxley-Simmons,1971

Myosin Motor Model(passive actin filaments)

The swinging cross-bridge theory

Pi

ATP

ActinMyosin V

Lever arm

“Apart from such quantitative uncertainties, there is always a possibility indeed, a probability that our present concepts are seriously incomplete or even wrong.”

AF Huxley Proc Roy Soc 2004 430-440

Commensurability At Work: The Third Architectonic Principle?

In our view, actin ‘thin filaments’can interconvert between the classical helical state and a ribbon state (having the same longitudinal spacing as the myosin headgroupson ‘thick filaments’).

A New Theory of Muscle Contraction

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Principle of Actin Motor

Force = 200 pN

Chik, Lindberg & Schutt, 1996Page, Lindberg & Schutt, 1998

ΔG is the free energy of ATP hydrolysis.

8.0x10-20 J/ATP molecule

Conformational change in actin in the direction of motion accompanies ATP hydrolysis

(a) Myosin induces a change in actin filaments.

(b) The change is propagated along actin filaments.

(c) ATP is hydrolyzed on actin.

(d) Force is generated as actinexpels phosphate.

Actin Motor Model

“Everything is movement; thought is a movement; life is based on movement; death is a movement to which the end escapes us. If

God is eternal, you may be sure he is always in motion. God is perhaps movement itself. That is why movement, like him, is

inexplicable – like him, profound, without limits, incomprehensible, intangible.”

Honore de Balzac (“Peau de Chagrin”)

”It is a landscape that offers itself up to contemplation like an endless plastic wonder whose beauty is as mysteriously static and changing as that of the stars.”

Mario Vargas Llosa (”Szyszlo”)Video:Andrew Matus

What Schrödinger perhaps should have known

Bernal & Fanchuchen had shown by x-ray crystallography that the protein coats of simple viruses (TMV & TBSV) had crystal-like order.

But, Irving Langmuir, the noted surface physicist, was championing the ‘cyclol’ hypothesis of Dorothy Wrinch, which may have seemed more compatible with the idea of quantum energy levels constituting a physical genetic coding substrate.

Muscle Fibers as Polanyi Engines

The external load is a constraint on the ATPase(s) transmitted directly to the ribbon-to-helix transition front via tropomyosin (The Fenn Effect)

Neural Growth Cone

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Andrew Matus, 1999

Mid-Ocean Hydrothermal Vents (FeS)

Fool’s Gold: Life’s First Perch?

Wächtershäuser, 1990

FeS + H2

S → FeS 2 ( pyrite ) + H 2

HCO3− + FeS + H2S → HCOO− + FeS2 + H2O

How did Manganese:Oxygen Clusters Evolve?

The original atmosphere was strongly reducing. About 3.4 billionyears ago oxygen began to appear, removing Fe++ by oxidation, leaving water as the most abundant reducing agent in the geosphere. Is it possible that MnO containing crystals were the first sites of water splitting?

Montmorillonite: Life’s First Gene?

Cairns-Smith, 1982

e-

e-

e-

The iron–sulfur clusters of the Fe-only hydrogenase from D. desulfuricans.

Active site is buried 30 Å below the surface of protein

Specific channels exist along which e- and H+ transfer

Surface

Evans & Pickett (2003) Chem Soc. Rev.

If attached to electrodes (F. Armstrong):

Diffusion-limited reversible H2 oxidationat finite overpotential

F-actin

Myosin ATP / ADP . PiPiADP

Rigor state

Lever arm

ATP

Myosin V

MreB Controls Shape

Doolittle’s Paradox

Actin and tubulin are amongst the most highly conserved eukaryotic proteins, varying by only 10% per billion years of evolution. Yet, the archael and bacterial homologs of actin and tubulin show structural but very distant sequence homology.

How can this be?

One possibility is that the rate of change of these proteins changed dramatically at a key point in their history, perhaps during the supposed ‘catastrophic loss of the cell wall’.

Doolittle, 1995

Yeast Phenylalanine tRNA

S.H. Kim et al. , 1974

Aminoacylation by Synthetases

“Everything is movement; thought is a movement; life is based on movement; death is a movement to which the end escapes us. If

God is eternal, you may be sure he is always in motion. God is perhaps movement itself. That is why movement, like him, is

inexplicable – like him, profound, without limits, incomprehensible, intangible.”

Honore de Balzac (“Peau de Chagrin”)

The Search for Our Pre-Cambrian Ancestor

APPROACH:

Determine expression maps in a developing hemichordate for orthologs of 22 neural patterning genes whose (spatial) domains have been carefully mapped in the chordate neural plate and nervous system.

Lowe et al, 2003

Mouse Forebrain Orthologs in S. kowalevskii

Lowe et al, 2003

Pervasive neurogenesis in ectoderm S. kowalevskii

Lowe et al, 2003

Neural Patterning from Compartments is Universal!

Lowe et al, 2003

Universal Neural Patterning

Lowe et al, 2003

“This abstract sculpture, made in the aftermath of WWII, suggests figures dangling in a cage. But if the strange forms evoke figures, it is not their

exterior, or outward appearance, but rather some unseen interior quality –something vital and sublime, some universal force.”

Joseph Jacobs

Two Ideas from Schrödinger’s book, What Is Life?

What physical structure could embody a plan for the whole organism, yet be stable enough to withstand incessant thermal bombardment?

T = τ exp (W/kT)

The Hammerhead Ribozyme

Borate Minerals Stabilize Ribose

S.A. Benner, Acc. Chem. Res. (2004)

Origins in Hydrothermal Vents

Photoelectrochemistry on Mineral Particles

Can Transition Ions Serve as Electron Donors to Phototrophs?

Electrochemical Potential

Fe2+ Fe3+ + e- -.75 V

Fe2+(CO32-) → Fe3+ (CO3

2-) + e- 0 V

Mn2+ → Mn3+ + e- -1.4 V

Mn2+(CO32-) → Mn3+(CO3

2-) + H+ + e- -0.55V

Carbonate complexation with M2+ transition ions greatly favors oxidation

The Actin Family

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Archael Bacterial Eukaryotic