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Paradigms    for  the  discrete  degrees  of  Divine  influx

PROTEIN  SYNTHESIS  AND  “FINE  TUNING”

Stephen  H.  Smith,    MD

“Proteins  are  subtle  and  delicate  things…”

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•  Enzymes

•  Signaling

•  Structural  

•  Transport

•  Regulatory

•  Storage

•  Immunity

Functions  of  Proteins

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•  Forces  at  work  operate  at  the  atomic  level

•  Apparent  causes  (forces)  in  nature  correspond  to  spiritual  qualities

•  Influx  “fine  tunes”  by  effects  on  the  electric  charge  

Why  look  at  Protein  Folding?

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“Understanding  the  spiritual  cascade  of  

discrete  degrees  behind  the  physical  

degree  of  life  may  be  a  framework  that  is  

useful  to  be]er  understand  what  is  still  

unknown  about  protein  structure,  

function  and  synthesis    Ian  Thompson,  PhD

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•  In  Vivo    (within  a  living  cell)

•  In  Vitro  (in  a  test  tube))

•  In  Silico  (computational)

Three  Approaches  to  the  Study  of  Protein  Synthesis

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•  19th  century  brewing  and  baking

•  Pasteur’s  discoveries

•  Pasteur  vs  Liebig                      Traube

Beginning  of  Modern  Protein  Science

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The  sequence  of  amino  acids  in  the  

primary  polypeptide  chain  determines  

the  final  folded  tertiary  form  and,  

therefore,  its  function.

“Anfinsen’s  Dogma”

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DNA                  mRNA                              Ribosome                              tRNA

What  Determines  the  Amino  Acid  Sequence?

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Stages  In  The  Formation  Of  Proteins

1.  Primary  =  polypeptide  chain 2.  Secondary  =  alpha  helix  and  beta  sheets 3.  Tertiary  =  “native”,  active,  fully  folded  

form 4.  Quaternary  =  combination  of  two  or  

more  discrete  polypeptide  chains

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The  end  (goal)  is  contained  within  the  cause          the  cause  

and  the  end  are  contained  in  the  

effect.    

 Discrete  Degrees

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•  With  only  100  amino  acids  

•  Trial  fold  once  every  ten  trillionth  of  a  

second    

•  1081  years  to  fold  successfully

•  Yet  protein  folding  takes  only  a  second!

“Levinthal’s  Paradox”

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•  “Bias”  in  the  pathways?  Yet  from  whence  cometh  the  “bias”?

•  “Funnel”  energy  landscape???  

Many  A]empts  to  Solve  Levinthal’s  Paradox

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Landscape  “Funnel”

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•  A  new  distinct  branch  of  science:  utilizing  chemistry,  biology,  and  physics  (both  classical  and  quantum  physics).

•  And  now,  for  the  first  time  theology!

The  Protein  Folding  Problem

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Causes  are  spiritual,  they  only  appear  to  be  from  

nature!

Key  Theological  Principle:

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All  forms  tend  toward  the  human  (form).

Key  Theological  Principle:

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Competing  Theories  of  Protein  Folding

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•  Thermodynamics:  Gibb’s  Free  Energy

•  Place  different  emphasis  on  hydrophobic-­‐‑hydrophilic  models

•  Research  is  largely  computational          and  increasingly  statistical

Forces  and  interactions  that  fold  and  stabilize  proteins  and  their  possible  correspondences!

Protein  Folding  -­‐‑  from  a  Theistic  Science  Perspective

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Electric  charges  implicit  in  the  forces  and  interactions  of  folding  can  be  fine  tuned  by  immediate  Divine  influx

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Protein  Folding  -­‐‑  from  a  Theistic  Science  Perspective

Which  forces  are  dominant  must  be  related  to  use!

Forces  and  Correspondences!

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•  van  der  Waals  forces

•  Hydrogen  bonds •  Ionic  bonds  (salt  bridges)

•  Covalent  bonds

•  Peptide  bonds

•  Hydrophobic  interactions

Hierarchy  of  Forces

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van  der  Waals  interactions  

•  Atoms  moving  in  close  proximity  generate  a  brief,  weak  a]raction

•  Almost  all  the  atoms  in  the  interior  of  the  molecule  are  involved

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van  der  Waals  interactions   •  Correspond  to  “bare  facts”?

•  Level  of  “effects”  only?

•  Corresponds  to  the  sensual/corporeal?

•  Like  the  waving  of  arms  and  hands  of  infants  exploring  their  limited  universe

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van  der  Waals  interactions  

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•  Very  common  in  proteins •  12  of  the  20  amino  acids  form            hydrogen  bonds

•  Asymmetric  electron  density  between  closely  aligned  atoms

Hydrogen  Bonds

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Hydrogen  Bonds

•  Corresponds  to  natural  knowledge  common  to  our  lives          “scientifics”?

•  Level  of  “apparent  causes  and  effects” •  A  union  of  good  and  truth  at  a  more  natural  (primitive)  level

•  Childhood  development  of  curiosity

Hydrogen  Bonds

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•  Ion  pairing  (salt  bridging)  oppositely  charged  amino  acid  side-­‐‑chains  are  in  close  spatial  proximity

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Ionic  Bonds

F=  q1q2  /  d2  ε

*    ε “dielectric  constant”  of  the  solvent (larger  epsilon  =  smaller  a]raction!)

Strength  of  an  Ionic  Bond:

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•  Salt  corresponds,  in  a  good  sense,  to  affection  for  truth

•  A  salt  bridge  might  therefore  correspond  to  a  relationship  based  on  affection  for  truth.

•  Now  at  the  level  of  “cognitions”? Slide  39

Salt  Bridges      (Ionic  bonds) •  Link  amino  acids  to  form  the          backbone  of  protein  structure •  Amino  (NH2)  and  Carboxyl  (COOH)  

of  adjacent  amino  acids  are  linked    and  a  molecule  of  H2O  is  released

•  Intermediate  between  a  single  and  double  bond

Peptide  Bonds

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Peptide  Bonds

•  A  tight  bond  that  resists  rotation

•  Corresponds  to  the  rational;  links  the  natural  mind  to  the  spiritual  mind  in  search  of  truth?

•  Think  of  Jacob  gripping  Esau’s  heel

Peptide  Bonds

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•  Share  electron  pairs  between  atoms

•  Greatest  between  atoms  of  similar  electro-­‐‑negativities

Covalent  Bonds

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•  Correspondence:  a  marriage  from  the  bond  of  good  and  truth?

•  Strong  bonds  with  limited  rotation

Covalent  Bonds

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Hydrophobic  Interactions

•  Hydrophobic  amino  acid  residues    are  found  mainly  in  the  core  of  the  functional  (native  state)  protein!

•  “Hydrophobic  collapse”  is  a  main  driver  of  folding

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•  Hydrophobic  lipid  (hydrocarbons)  correspond  to  love!

•  Like  the  hydrophobic  amino  acids  in  the  folded  state,  love  is  interior!

•  Hydrophobic  interactions  with  water    are  primary  drivers  in  folding!

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Hydrophobic  Interactions

•  Quantum  physics  of  water  key  to  understanding  the  folding  mechanism!

•  The  dielectric  constant  of  the  solvent  and  the  interior  environment  =  an  opportunity  for  “fine  tuning”!

 Hydrophobic  Amino  Acids    and  Water

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•  Long  range  interactions •  Solitons •  The  cell  as  an  “electrome”

New  Horizons!

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“Everything  in  the  universe  that  is  in  harmony  with  God’s  plan  relates  to  goodness  and  truth.”

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New  Jerusalem  and  its  Heavenly  Doctrine  11      

 “Also,  they  do  not  know  what  correspondence  is  and  what  influx  is,  and  that  when  the  spiritual  flows  into  the  organic  forms  belonging  to  the  body,  it  establishes  the  living  workings  such  as  occur  there.  Nor  do  they  know  that  without  such  influx  and  correspondence  not  even  the  smallest  parts  of  the  body  can  have  life  or  be  set  in  motion.”

Arcana  Coelestia  3629

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Chaperone  Proteins

•  AKA  “heat  shock”  or  “stress”  proteins

•  Major  family  groups  based  on  molecular  weight  in  kDa

•  hsp  110,  hsp  90,  hsp  70,  hsp  60,  small  hsps  (14-­‐‑50  kDa)

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Assist  as  “nursemaids”  for  nascent  polypeptide  chains  so  they  fold  quickly  and  correctly.

Chaperone  Proteins

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Prevent  newly  formed  proteins  from  aggregating

Chaperone  Proteins

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 Degrade  misfolded  proteins

Chaperone  Proteins

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Transport  proteins  to  the  lysosome  for  recycling

Chaperone  Proteins

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•  Correspondence  to  celestial  angels,  spiritual  angels  and  good  spirits?

•  Celestial  angels  relate  to  the  hydrophobic  interactions,  the  spiritual  to  the  electrostatic?

Chaperone  Proteins

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Heat  Shock  Proteins

•  Increase  in  response  to  thermal  and  other  stress

•  Protect  proteins  from  denaturation

An  additional  role  of  chaperone  protein  

molecules!

“Behold  I  Make  All  Things  New”

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•  May  preserve  a  totally  new  protein  for  some  future  use!

•  How  does  it  recognize  it  as  potentially  useful?

Chaperone  Proteins

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“…    To  enable  the  cause  to  exist  the  end  must  act  on  the  level  where  the  cause  belongs,  calling  on  assistant  means  to  help  it  –the  end-­‐‑  to  bring  the  cause  into  existence,  and  to  enable  the  effect  to  exist  the  cause  likewise  must  act  on  the  level  where  the  effect  belongs,  by  calling  on  assistant...”

Arcana  Coelestia  5131

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“…Thus  the  whole  body  is  an  organ  

composed  of  the  deepest  arcana  belonging  to  

everything  which  exists  within  the  natural  

world,  and  its  formation  is  determined  by  

hidden  forces  by  which  all  things  act  and  the  

wonderful  manner  in  which  they  flow.”

Arcana  Coelestia  4523

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Fine  Tuning  

End  è  Cause  è  Effect

é

Transient,  small  fluctuations  in  constants  of  nature

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 “The  existence  of  life  as  we  know  it  

depends  delicately  on  many  seemingly  

fortuitous  features  of  the  laws  of  physics  

and  the  structure  of  the  universe.”                                                               Paul  Davies,  

                                               The  Mind  Of  God   Slide  63

Fine  Tuning   “There  are  three  types  of  change  to  consider.  Tiny  infinitesimal  changes  are  possible.  If  we  change  the  value  of  the  fine  structure  constant  only  in  the  20th  decimal  place  there  will  be  no  bad  consequences  for  life…if  we  change  it  by  a  very  small  amount,  say  the  2nd  decimal  place,  then  the  changes  become  more  significant.  

Fine  Tuning

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Continued  on  next  slide

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Properties  of  atoms  are  altered  and  complicated  processes  like  protein  folding  or  DNA  replication  may  be  adversely  affected.”

Fine  Tuning

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John  Barrow The  Constants  of  Nature

Continued  from  last  slide

Fine  Structure  Constant

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“And  because  there  must  be  a  continuous  connection  with  the  spiritual  world  in  order  that  every  single  thing  may  be  kept  in  being,  or  constantly  come  into  being,  it  follows  that  the  purer  or  more  interior  things  within  the  natural  order,  and  consequently  within  the  human  being,  spring  from  that  world,  and  the  purer  or  more  interior  things  are  forms  such  as  are  able  to  receive  influx…”

Arcana  Coelestia  4524

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