Mailing List complex-science@necsi.org Message #4682

From: "Michael Grant" <Michael.Grant at colorado.edu>
Sender: <yaneer at necsi.org> (Yaneer Bar-Yam)
Subject: RE: "Fuzzy molecular machines"
Date: Wed, 05 Mar 2003 16:07:31 -0500
To: complex-science
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In reply to Gavin's question/statement about the importance of feedback cycles for biological entities, I can point to two articles that Doug Robertson and I published on just this point.  There are others of course although biologists have come to this view somewhat belatedly.
 

Robertson, D. and M. C. Grant.  1996. Feedback and chaos in Darwinian evolution, Part I: Theoretical considerations.  Complexity 2:10-14 

Robertson, D. and M. C. Grant.  1996. Feedback and chaos in Darwinian evolution, Part II:  Numerical modeling. Complexity 2: 18-30

 

Michael Grant

Hi Val & Sung

 

John Holland has developed an if-then model called Echo if I remember correctly.

 

I have a bit of an issue with this type of model, I firstly think that in your circumstances you may have far more complicated logic like parallel processing bi-conditional variables, e.g. if-and-only-if is bi-conditional whilst if-then is only conditional in one direction. That is a whole number of things working in parallel and conditional on reciprocity. Of course feedback loops change a model drastically.

 

I am of the opinion that if-then rules can not cover enough of the fuzzy ground. If-then rules just do not have the conditions of a cybernetic loop; it assumes only that this causes that, and not the issue of reciprocity which is so important in the biological sense and also in the human cognitive sense (information). Only reciprocity can create novelty and diversity ie the feedback having the opportunity to change the being (form-shape-morphology-structure).

 

In communication theory to change (transform). The output/input = the reciprocal of the feedback transfer function. So the feedback cycle can quite easily drown out noise from an input signal. This must (?) be important in biological entities.

 

Kindest

gavin

 

 

 

-----Original Message-----
From: complex-science at necsi.org [mailto:complex-science at necsi.org] On Behalf Of Sungchul Ji
Sent: Monday, 3 March 2003 6:01 a.m.
To: complex-science at necsi.org
Subject: "Fuzzy molecular machines"

 

Val,
    Thanks for your thoughtful response.  Let me try to answer
some of your questions:

>   You present an interesting line of reasoning which seems
>to be non-contradictive logically.  Your focus is on a
>specific unit ('biopolymer'), how it 'works' and how cell
>coordinates activities of zillion polymers.  You use 'fuzzyness'
>to mimic (conformational) plasticity of biopolymers.

    Yes.  I am assuming that a protein, P, can be treated
as a fuzzy set, whose members are determined not by their
sequences themselves but by their 3-dimensional shapes
(largely but not entirely determined by their sequences) which
ultimately determine their biological functions.  I know this is
quite a departure form the traditional view that protein structures
are based on amino acid sequences alone.  My shape-based
definition of proteins is in part supported by the finding that two
different amino acid sequences of receptors and enzymes can
often manifest identical functions and shapes.

>    However, the whole idea of (macromolecular machine
>seems to me not quite compatible with living cell.

    I am viewing a living cell as an organized system of N molecular
machines, where N can vary considerably, from a few hundreds to
millions or more.  My current hypothesis is that each such molecular
machine can be represented as a fuzzy if-then rule, and hence a
living cell may be treated as a "fuzzy system" composed of N such
fuzzy if-then rules.  It is interesting to note that human-made "fuzzy
machines" like washing machines, digital cameras, etc., are fuzzy
systems based on only about a dozen fuzzy if-then rules [B. Kosko,
1993].  In contrast, I think an average living cell may contain millions,
if not billions, of molecular if-then rules and as a result can be several
orders of magnitude more intelligent than ordinary human-made machines.

>Cell itself perhaps could be considered as a sort of machine
>due to its highly coherent spatial and temporal organization.

    I would agree with you whole heartedly.

>Hardly, there are separate molecules/machines in cell
>(like there are no atoms in molecules).

    You have cited a good analogy here -- atoms and molecules.
Depending on one's view, one can say that molecules are indeed
made out of atoms, just as words are made out of letters.  Of
course, atoms are not separate from molecules of which they are
parts but the physicochemical properties of molecules are largely
determined by the atomic structures of component atoms, as you
know.  Quantum mechanically, molecular orbitals can be
built through linear combinations of atomic orbitals.
    It is in this sense that I am saying that enzymes constitute the
component molecular machines of the cell.  Similarly, Boeing 747,
to me, is a machine made out of millions of smaller component
machines.

>Cell is a highly dynamic,
>integral, memory-based, env-sensitive and memory-driven system
>in its responses to the env.  There is no randomness in its responses.

Do you think cell's responses are then deterministic?
According to the cell language theory [BioSystems 44:
17-39 (1997)], the cell is a rule-governed creative system
(called "creatons") and hence its behaviors, although constrained
by a set of deterministic rules, can exhibit novelty unpredictable
from any internal rules and therefore creative.

>Its plasticity or flexibility is due to the fact that energy
>is *not* dominant parameter in its behavior - within the same
>energy there are zillions of (conformational, rotational,
>vibrational, and mixed) states of the cell as a whole.

    Energy is a necessary but not a sufficient condition for cellular
activities. I would not underestimate the fundamental importance
energy in all matters concerned with molecular and cell biology.
Otherwise I am afraid we will lose sight of the difference between
artifical life and real life on the one hand and between artifical
intelligence (AI) and real intelligence (RI) on the other.

>The state means the integrity, and that's is a definition
>of a biological cell.  So, a *cell* is a machine, if you will.
>And it is driven by the env *and* its own control memory which
>is programmable in turn by the env (feedback driven).

    A cell is a system of molecular machines driven by two things:
FREE ENERGY and INFORMATION encoded in DNA as
if-then rules [Comm. Toxicol. 5(6): 571-585 (1997)].
Environmental factors are taken into account in the "if" part and
the genetic information in the "then" part of the if-then rules.

>    DNA is only a part of a cell, its core control engine;
>however, the control functions are rather distributed over the cell
>and integrated with the expression pipeline again stressing the
>importance of 3D matrix/pipeline-like dynamic coherent organization.

    I agree.  This is why I cannot accept the naive notion of "DNA-
computers" and "DNA computing" frequently discussed in the literature.
Without the cell, DNA cannot do any computing, just as without the
hardware, Windows cannot do anything useful.

>    The language of a cell, if at all, is the one of communication
>between the env and the cell.  Its semantics include both highly
>specific signals which are then expressed in highly specific
>proteins *and* highly non-specific signals (say, thermal or whatever
>shock) which are then expressed in a wide spectrum of (non-specific)
>proteins; as well as signals in-between the mentioned extremes.
>So, the if/then response is actually the case of specific signal/
>response only.

   According to the FAT (fuzzy approximation theorem) of Kosko,
a system of fuzzy if-then rules can approximate any systems and
mathematical functions, presumably both crisp and fuzzy [B. Kosko,
Fuzzy Thinking, Hyperion, New York, 1993, pp. 167-171]. 

>The non-specific signal logic still remains to be
>discovered in computer logic (like a delta-function invokes a mix/
>combination of frequency components); same for in-between signals.

    I speculated in [Molecular Theories of Cell Life and Death,
ed. S. Ji, Rutgers Univ. Press, 1991, pp. 132-3] that bacterial cell
membrane may contain nonspecific receptors for water.  This "water
receptor", if found, is may be immune to point mutations as long as the
amino acid substitutions conserve the hydrophobicity of the receptor.

> These comments of course do not prove anything but hopefully
>make the discussion more balanced.

    I think your insightful comments are thought provoking.

    With all the best.

    Sung
    ____________________________________
    Sungchul Ji, Ph.D.
    Department of Pharmacology and Toxicology
    Rutgers University
Piscataway, N.J. 08855
 

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