<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OJBIPHY</journal-id><journal-title-group><journal-title>Open Journal of Biophysics</journal-title></journal-title-group><issn pub-type="epub">2164-5388</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ojbiphy.2013.34032</article-id><article-id pub-id-type="publisher-id">OJBIPHY-38166</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biomedical&amp;Life Sciences</subject><subject> Physics&amp;Mathematics</subject></subj-group></article-categories><title-group><article-title>
 
 
  Comment on a Paper: “Ben-Naim’s ‘Pitfalls’: Don Quixote’s Windmill”, by Y. Fang, Open Journal of Biophysics, 2013, 3, 13-21
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>rieh</surname><given-names>Ben-Naim</given-names></name><xref ref-type="aff" rid="aff1"><sub>1</sub></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Physical Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel</addr-line></aff><author-notes><corresp id="cor1">* E-mail:<email>arieh@fh.huji.ac.il</email></corresp></author-notes><pub-date pub-type="epub"><day>29</day><month>07</month><year>2013</year></pub-date><volume>03</volume><issue>04</issue><fpage>275</fpage><lpage>276</lpage><history><date date-type="received"><day>February</day>	<month>28,</month>	<year>2013</year></date><date date-type="rev-recd"><day>April</day>	<month>5,</month>	<year>2013</year>	</date><date date-type="accepted"><day>May</day>	<month>7,</month>	<year>2013</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
   This article is a response to Fang’s article which criticizes statements never made by Ben-Naim and never appeared in the literature. 
     
 
</p></abstract><kwd-group><kwd>Protein Folding; Leviathan Paradox</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>The article by Fang [<xref ref-type="bibr" rid="scirp.38166-ref1">1</xref>] deals with purported claims attributed to Ben-Naim’s articles [2-4]. Unfortunately, the whole article is based on statements, presented as if they were quotations from Ben-Naim’s articles, when in fact, were never ever made by Ben-Naim.</p><p>To start with, the title of the article is ambiguous. Does the author mean that Ben-Naim is Don Quixote, or that the “pitfalls” discussed in the articles are the “Windmill”?</p><p>In the following pages, I shall present only a few examples. Interested readers can find many more examples in this article [<xref ref-type="bibr" rid="scirp.38166-ref1">1</xref>].</p></sec><sec id="s2"><title>2. In the Abstract the Author States</title><p>“Ben-Naim, in three articles dismissed and ‘answered’ the Levinthal paradox…”</p><p>Indeed, I dismissed the Levinthal paradox in my articles [2,5], but I never “answered” the “Levinthal paradox”. I was careful enough to make it clear that I was answering the Levinthal question [<xref ref-type="bibr" rid="scirp.38166-ref4">4</xref>], and not the paradox [<xref ref-type="bibr" rid="scirp.38166-ref2">2</xref>]. This is an important distinction overlooked and misunderstood by the author.</p></sec><sec id="s3"><title>3. In the Abstract the Author States</title><p>“He claims (Ben-Naim) no existence of Gibbs energy formula <img src="8-1850060\beb267eb-43a9-4b85-9a9f-b3b393dedbc5.jpg" />.”</p><p>This is not true. In all my writings I discussed the function <img src="8-1850060\079af4a9-d39c-492f-8f5a-e52d26e0c36e.jpg" />, and I never said that such a formula does not exist! For more details, the reader is referred to my recent monograph [<xref ref-type="bibr" rid="scirp.38166-ref6">6</xref>].</p></sec><sec id="s4"><title>4. In the Abstract and in the Article the Author Claims</title><p>“His minimum distribution <img src="8-1850060\f6b6c419-247a-4f79-8195-557b0319da30.jpg" /> is wrong.”</p><p>I never said that. What I was talking about is the distribution <img src="8-1850060\54f29390-6b28-4c00-9fd0-8c83147ec5b5.jpg" /> that minimizes the Gibbs energy functional (see below). I have no idea what the “minimum distribution <img src="8-1850060\1dde81b0-0822-4340-b5c8-7aee4c3824f6.jpg" /> is, which the author claims to be “mine.”</p></sec><sec id="s5"><title>5. In Section 1 of the Article, the Author Writes</title><p>“Here Ben-Naim implies that the conformation of a protein should not be the variable of the Gibbs energy.”</p><p>Again, this is not true. The so-called Gibbs energy landscape is a function of the conformation of the protein. I never claimed, nor implied that the “conformation of a protein should not be the variable of the Gibbs energy”.</p></sec><sec id="s6"><title>6. Another Quotation from Section 1 of the Article [<xref ref-type="bibr" rid="scirp.38166-ref1">1</xref>]</title><p>“Even knowing what is Ben-Naim’s minimum distribution, we still do not know what the three dimensional shape of the native structure.”</p><p>Again, I never talked about “Ben-Naim’s minimum distribution”. I have no idea what the “Ben-Naim’s minimum distribution” is. As I noted above what I talk about is the distribution <img src="8-1850060\11da26f4-46b2-41b1-8219-5e3ca685a865.jpg" /> which minimizes the Gibbs energy functional, under a given environment <img src="8-1850060\c6fc3089-6dee-4c70-b11e-4c7eecc4ca65.jpg" />. If one knew this distribution, then one could tell which conformations are more probable than the others under the given environment.</p></sec><sec id="s7"><title>7. In Section 2, the Author Writes</title><p>“All previous attempts of deriving the Gibbs energy formula, including Ben-Naim’s, missed the goal of identifying the three dimensional structure of a native protein.”</p><p>This quotation is doubly misleading. In a previous quotation above, the author claims that Ben-Naim “claims no existence of Gibbs energy formula”. If I claim that “Gibbs energy formula does not exist” (which I never did, see above), how then could I even attempt (among others), to derive the Gibbs free energy formula? In this quotation the author contradicts his previous statements. The truth is that I never denied the existence of the Gibbs energy formula, nor did I ever attempt to derive the Gibbs free energy formula. Therefore, all of the criticisms are addressed to claims that were never made by me in any of my writings.</p></sec><sec id="s8"><title>8. Finally, in His Conclusion the Author Writes</title><p>“Ben-Naim’s minimization at <img src="8-1850060\5bcc180e-a502-481d-b651-06fa46ddd964.jpg" /> is analyzed and dismissed because it predicts that at equilibrium every possible conformation R will have the same probability.”</p><p>This is again a criticism of a claim I never made. The parameter R in <img src="8-1850060\c5e1baf0-0b18-417c-b34c-15dd28a1aba1.jpg" /> is the location of the center of a simple spherical solute in a solution. This is clearly stated in my article. The function <img src="8-1850060\53d3dbfb-5324-4a9d-9db3-5a450821938b.jpg" /> is the equilibrium density function for the locations of the solute particle. This is an exact result. It has nothing to do with proteins! Yet the author criticism is “Ben-Naim claims that <img src="8-1850060\2dfb02b8-cebc-4923-a176-16a9a4f12772.jpg" /> for any conformation R”, a claim attributed to me but which I never made.</p><p>There are many more misquotations and false statements in this article. I believe the examples provided above suffice to demonstrate the character of this article. It is also clear that the author of Reference [<xref ref-type="bibr" rid="scirp.38166-ref1">1</xref>] did not understand any of my articles I should end with a note on the author’s claim of achievements.</p><p>Finally, the author claims that he demonstrates how “to apply quantum statistics to derive the Gibbs energy formula <img src="8-1850060\ee65409d-1243-450d-9304-aaf9c0a761cb.jpg" />, and the folding force”. Both of these are not delivered. All he did was to rewrite the Gibbs energy function <img src="8-1850060\152c6f35-7170-49a2-a7e1-0d3fb21178f3.jpg" /> in terms of the entropy function <img src="8-1850060\f94fb734-e4ec-4917-bd09-763c06543181.jpg" />, the volume function <img src="8-1850060\12106e1f-3ed0-4e38-9849-d618384faeed.jpg" /> and the energy function <img src="8-1850060\14d7ece6-d028-4530-8af0-14f860870da3.jpg" /> but not an explicit Gibbs energy function <img src="8-1850060\f2db376b-473e-476c-b011-2ab13e49cf3c.jpg" />. His achievement is summarized in Section 7.4 as:</p><p>“Thus, by (27) we obtain the Gibbs free energy <img src="8-1850060\aa554df4-2882-4ec5-a755-03b5aedc2680.jpg" />…</p><p><img src="8-1850060\7e374d48-e43e-4e38-89b3-d3d8c2fe277e.jpg" />.”</p><p>Which is a well known identity.</p></sec><sec id="s9"><title>9. Conclusion</title><p>This article does not provide anything new, and the criticisms it raises are addressed to statements that I never made.</p></sec><sec id="s10"><title>REFERENCES</title></sec></body><back><ref-list><title>References</title><ref id="scirp.38166-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Y. Fang, “’Ben-Naim’s “Pitfall’: Don Quixote’s Windmill,” Open Journal of Biophysics, Vol. 3, No. 1, 2013, pp. 13-21. 
http://dx.doi.org/10.4236/ojbiphy.2013.31002</mixed-citation></ref><ref id="scirp.38166-ref2"><label>2</label><mixed-citation publication-type="other" xlink:type="simple">C. Levinthal, “How to Fold Graciously,” M?ssbauer Spectroscopy in Biological Systems Proceedings, Vol. 67, No. 41, 1969, pp. 22-26. </mixed-citation></ref><ref id="scirp.38166-ref3"><label>3</label><mixed-citation publication-type="other" xlink:type="simple">A. Ben-Naim, “Levinthal’s Paradox Revisited and Dismissed,” Open Journal of Biophysics, Vol. 2, No. 2, 2012, pp. 22-32. http://dx.doi.org/10.4236/ojbiphy.2012.22004</mixed-citation></ref><ref id="scirp.38166-ref4"><label>4</label><mixed-citation publication-type="other" xlink:type="simple">A. Ben-Naim, “Pitfalls in Anfinsen’s Thermodynamic Hypothesis,” Chemical Physics Letters, Vol. 511, No. 1-3, 2011, pp. 126-128.  
http://dx.doi.org/10.1016/j.cplett.2011.05.049</mixed-citation></ref><ref id="scirp.38166-ref5"><label>5</label><mixed-citation publication-type="other" xlink:type="simple">A. Ben-Naim, “Levinthal’s Question Revisited, and Answered,” Journal of Biomolecular Structure and Dynamics, Vol. 30, No. 1, 2012, pp. 113-124.  
http://dx.doi.org/10.1080/07391102.2012.674286</mixed-citation></ref><ref id="scirp.38166-ref6"><label>6</label><mixed-citation publication-type="other" xlink:type="simple">A. Ben-Naim, “The Protein Folding Problem and Its Solutions,” World Scientific, Singapore, 2013. 
http://dx.doi.org/10.1142/8627</mixed-citation></ref></ref-list></back></article>