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Effect of chiral helical force field on molecular helical enantiomers and possible origin of biomolecular homochirality
Medical Hypotheses (1998) 51, 125-128 © Harcourt Brace & Co. Ltd 1998
Effect of chiral helical force field on molecular helical enantiomers and possible origin of biomolecular homochirality Y. J. HE *'t, F. QI t, S. C. QI* *Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA; tlnstitute of Biophysics, Academia Sinica, Beijing, P. R. China; CDepartment of Technical Physics, Peking University, Beijing, P. R. China. Correspondence to: Yu Jian He, 335 Grove Avenue, Falls Church, VA 22046, USA. (Phone~Fax: +1 703 532 4096; e-mail: [email protected])
Abstract - - Biomolecular homochirality means that the amino acids in proteins, and sugars in nucleic acids, occur in one form: amino acids in L-form and sugars in D-form. So far, the reason w h y these molecules have such uniform chirality is not known. In this paper, it is suggested that a net natural chiral right-handed helical force field, produced by the Earth's orbital chirality (EOC), could affect the stability of molecular helical enantiomers and make the right-handed helical enantiomers more stable than their left-handed enantiomers, so terrestrial biological systems must select both right-handed helical nucleic acids based on D-sugars, and proteins based on L-amino acids. In given conditions, the maximum energy difference between biomolecular helical enantiomers (AEr, ax = IE~eft- E,~ghtl) caused by the EOC may be calculated theoretically to be in the order: B-DNA > A-RNA > A-DNA >> (~-protein > [~-protein. Our experimental results strongly supported the hypothesis that the EOC could cause the spontaneous selection and amplification of right-handed helical enantiomers and could be the origin of homochirality on the Earth.
Introduction On the Earth, biological systems are based on D-sugars and L-amino acids. The origin of biomolecular homochirality, a classical problem, has always attracted interest, and a variety of different physical and chemical phenomena have been suggested as explanations of its origin (1-3). So far, convincing theory and experiment on the origin of homochirality are still lacking (1). Norden thought that the microscopic selections are not genuine selections, because the final sense of asymmetry is determined by chance,
in other words the initial choice is random, whereas it is directed in the macroscopic selection (2). Thermodynamic and kinetic analysis shows clearly that the mechanistic selection efficiency is not of primary importance but that even very weak preference can give an amplification mechanism and complete selection in time (2,3).
Hypothesis and calculations As we know, L-amino acid peptides form righthanded or-helices, and D-ribose polynucleotides tend
Received 14 March 1997 Accepted 13 May 1997
125
126
MEDICAL HYPOTHESES
to form right-handed helices; the opposite isomers tend to form left-handed helices (4). In a-helices of L-amino acids, the incorporation of an occasional D-amino acid will be disfavored by steric hindrance and an a-helix of a racemic poly-amino acid will be significantly less stable, correspondingly, since the incorporation of L-ribose would inevitably disrupt the D-structure, the DNA helices must always contain a single form of enantiomer (2). In principle, there cannot be any energy difference between chiral helical enantiomers under achiral conditions (Fig. 1a). What is the natural macroscopic cause that gave rise to the preference of both right-handed helical nucleic acids and proteins on Earth? In the studies on the cause of physical and organic chirality, the possible importance of a 'dissymmetric universe' was first suggested by Pasteur (2,3). The solar system as a whole is asymmetric, for it is not superposable on its mirror image, and so spin and orbital rotational forces may be the cause of physical and organic chirality (3). In fact, the concepts of the protein ahelix and DNA right-handed helix were not formally pointed out until the early 1950s. Pasteur had not considered the relationships between a chiral helical force field and molecular helical enantiomers to explain the origin of biomolecular homochirality, and neither had the latter researchers, so far as we know. It is suggested here that the cause, and the origin of homochirality, may be the Earth's orbital chirality (EOC). The EOC is mainly created by two natural helical motions: both the Earth's right-handed helical rotation around its spin rotation axis and the Earth's right-handed helical revolution around the Sun. When combined with the Sun's motion in space and time, both the Earth's motions (rotation and revolution) are chiral and helical (Fig. 2) - - a fact which one often ignores! The EOC produces a net natural and macroscopic chiral right-handed helical force field over the Earth and may result in an intrinsic energy difference (AE) between helical biomolecular enantiomers (Fig. lb). At a given point on the Earth's surface, there should be an angle ((~) between the centrifugal force
of the Earth's spin rotation (Fee) and that of the Earth around the Sun (Fes). Taking into account the obliquity of the ecliptic (tp = 23.45 °) and the Earth's motion, etc. (Fig. 3b) (5), the total centrifugal force (Fete) should be given by: F¢o~= [FZee+ FZes- 2F~ F~s cos (180 ° -t~)] '~ (1) Because 0 ___t~ < 180 °, -1 < cos (180 ° - ¢)) _< 1, and the maximum Fmaxeoc= [F2ee+ F2es + 2F~ Fes]'~ = (F~ + Fes), the maximum energy difference (AEr~x) between right- and left-helical enantiomers at a point on the Earth's surface should be given by: AEmax = 2(1/2)N (Rm/COS20m)(Fee + Fe~) = N m (Rm/cOS20m)[4~2ReJ(Tee) 2 +
4x2Res/(Tes) 21
(3)
< (3.97 × 10-2) N m (Rm/COS20m) (J/molecule)
Left-handed E~e~ Right-handed enantiomers
~Oleft Left-handed enantiomers a
(4)
where N is the number of residues in a molecular helix, m is the residue's average mass (kg), R m is the radius of a molecular helix, 0m is its helical angle (Fig. 3a), and R~ and Re~ are the shortest distance from the point on the Earth's surface to the Earth's axis and the Sun, respectively; Te~ (1 day) and T~s (365 days) are the period of the Earth's rotation and revolution, respectively. When N is 1, AEm~xwould be the energy difference between either amino acid or nucleotide residue enantiomers. At a given point on the Earth's surface, according to the molecular structural parameters (Rm, 0m, m, etc.) (6) and equation (4), the AEmax between biomolecular helical enantiomers may be calculated theoretically to be in the order: BDNA > A-RNA > A-DNA >> a-protein > ~-protein. Moreover, in equation (1), as time progresses, the will make the F~oc change periodically in Tee and Te~, which may periodically change the activation energy of biomolecular reactions in living systems as well. In theory, it may be able to explain the biorhythms of biological systems on the Earth. In addition, we are interested in whether the macroscopic asymmetric helical EOC force field may affect the motion of the fundamental particles which also have an intrinsic handedness, whether there are any rela-
enantiomers
EOright
(2)
AE
T Energy
EriQht Right-handed enantiomers b
Fig. 1 The possibleenergylevelof helicalenantiomersin (a) an achiralforcefieldand (b) fight-handedhelical EOC forcefield.
127
CHIRALHELICALFORCEFIELDAND BIOMOLECULARHOMOCHIRALITY (~19.7 km/s) Sun (~35.7 kin/s) arth
Time (s)
,4 Earth Sun a
b
Fig. 2 Schematic description of the Earth's orbital chirality (EOC): (a) the Earth's circular motion around the sun; (b) the Earth's fight-handed helical revolution around the Sun. Circular motion and the right-handed helical motion of any point on the Earth's surface (except the poles) around the earth's rotation axis (not iUustrated) are similar to (a) and (b), respectively, i.e. in the figure, the label 'any point on the earth's surface' (except the poles) and 'Earth's rotation axis' could replace the labels 'Earth' and 'Sun', respectively. In consideration of all the above complex motions, the motion of any point on the earth's surface (except the poles) is a super helix in space and time.
Direction of EOC's helix axis Helix axis
Direction of the Sun's motion
l
Direction of the Earth's axis
¢p(23.45o)
\
T
(180°-~)
Sun
a
b
Fig. 3 (a) Definition of some parameters for a right-handed helix, tan 0 = P / 2 n R , for helical angle 0. V is the helical velocity of either the residue or the earth (or the point on the earth's surface, etc.) along its own helical orbit; the circular motion velocity around its helix axis is Veto= (V cos0), which produces a centripetal (or centrifugal) force in the helix: F = m (Vcm)E/R = m ( V c o s O ) 2 / R = m 4n'2R/T 2, where Tis the helical period. (b) Schematic description of the earth's obliquity (i.e. the obliquity of the ecliptic, tp = 23.45 °) and the angle (~) between F~ and F,s at a given point on the earth's surface where biomolecular helices occur at a given time (t). tionships b e t w e e n the E O C and parity-violating w e a k interaction, etc. T h e s e interesting questions h a v e b e e n studied and discussed e l s e w h e r e (7).
Experimental support As is w e l l k n o w n , under certain conditions, the l o w e r f l u o r e s c e n c e intensity o f e t h i d i u m b r o m i d e
(EB) in the presence o f D N A is, the less stable is the right-handed helical D N A - E B c o m p l e x (6,8). A s can be seen f r o m Fig. 4b, the external left-handed helical force destabilizes the right-handed helical d[G3T4G3].d[C3AaC3]-EB c o m p l e x ; then, as scanning t i m e progresses, the natural right-handed helical force field o f the E O C replaces the disappeared external left-handed helical force, resulting in increased f l u o r e s c e n c e intensity o f the right-handed helical
1 28
MEDICAL HYPOTHESES
tions, and the right-handed helical force of the EOC and the external right-handed helical force stabilizes the right-handed conformations. Therefore, the righthanded helical nucleic acid and protein enantiomers should be stabilized and selected by the natural righthanded force field of the EOC, which is the origin of homochirality on the Earth.
1 095 000
1 090 000 =.
o
1 085 000
E
,~ 1 080 000 o o 1 075 000 1 070 000
Conclusions
1 065 000
2'o
2'5
3'0
"13me (s)
Fig. 4 The time scanning curves of fluorescence intensity of DNA-EB solution at 25°C (~,= 520 nm, 2%,.= 615 nm). (a) Before helical rotation in the presence of EOC; (b) after external left-handed helical rotation (relative to the EOC's helical direction) at ~2000 r.p.m, for ~10 rain (R = 6 cm). (c) After external right-handed helical rotation [condition same as (b)]. Sample: 22.5 p2Vlbps d[G3T4Gs].d[C3A4C3]right-handed duplex in 50 mM NaAc/HAc-H20 buffer containing 45 IxM EB, pH 6.
In summary, the Earth's orbital chirality (EOC) produces an effective chiral fight-handed helical force field over the earth. It makes right-handed helical enantiomers more stable than the corresponding left-handed helical enantiomers, so terrestrial living systems must select both right-handed nucleic acids based on D-sugars and right-handed proteins based on L-amino acids.
References DNA-EB complex solution; the fluorescence intensity approaches its value before external helical rotation (Fig. 4a) after a scanning time of about 12 s. Fig. 4c shows that the external fight-handed helical force almost fails to change the fluorescence intensity of the right-handed helical DNA-EB complex, because the natural right-handed helical EOC has stabilized the latter. There are similar results from right-handed RNaseA and poly-(A).poly (U)-EB solution, and the longer helical rotation time results in larger changes of fluorescence intensity of proteins or nucleic acids-EB complex solution (data not shown). All these experimental data strongly demonstrate that the left-handed helical force destabilizes the fight-handed conforma-
1. Cohen J. Getting all turned around over the origins of life on earth. Science 1995; 267: 1265-1266. 2. Norden B. The asymmetry of life. J Mol Evol 1978; 11: 313-332. 3. Mason S F. Universal dissymmetry and the origin of biomolecular chirality. Biosystems 1987; 20: 27-35. 4. Lacey J C, Wickramasinghe W S M D, Cook G W, Anderson G. Couplings of character and of chirality in the origin of the genetic system. J Mol Evol 1993; 37: 233-239. 5. Shan Dong Science and Technology Press, eds. Handbook of Zhong Xue Xue Xi [in Chinese]. Shandong, P. R. China: Shan Dong Science and Technology Press, 1982: 260--266, 274, 281,532, 541,542. 6. Saenger W. Principles of Nucleic Acid Structure. New York: Springer-Verlag, 1984: 250, 350--353. 7. He Y J, Qi F, Qi S C. Periodicity of the earth's orbital chirality and possible mechanism of biological rhythm, submitted. 8. Scaria P V, Shafer R H. Binding of ethidium bromide to a DNA triple helix. J Biol Chem 1991; 266(9): 5417-5428.
Effect of chiral helical force field on molecular helical enantiomers and possible origin of biomolecular homochirality Y. J. HE *'t, F. QI t, S. C. QI* *Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA, USA; tlnstitute of Biophysics, Academia Sinica, Beijing, P. R. China; CDepartment of Technical Physics, Peking University, Beijing, P. R. China. Correspondence to: Yu Jian He, 335 Grove Avenue, Falls Church, VA 22046, USA. (Phone~Fax: +1 703 532 4096; e-mail: [email protected])
Abstract - - Biomolecular homochirality means that the amino acids in proteins, and sugars in nucleic acids, occur in one form: amino acids in L-form and sugars in D-form. So far, the reason w h y these molecules have such uniform chirality is not known. In this paper, it is suggested that a net natural chiral right-handed helical force field, produced by the Earth's orbital chirality (EOC), could affect the stability of molecular helical enantiomers and make the right-handed helical enantiomers more stable than their left-handed enantiomers, so terrestrial biological systems must select both right-handed helical nucleic acids based on D-sugars, and proteins based on L-amino acids. In given conditions, the maximum energy difference between biomolecular helical enantiomers (AEr, ax = IE~eft- E,~ghtl) caused by the EOC may be calculated theoretically to be in the order: B-DNA > A-RNA > A-DNA >> (~-protein > [~-protein. Our experimental results strongly supported the hypothesis that the EOC could cause the spontaneous selection and amplification of right-handed helical enantiomers and could be the origin of homochirality on the Earth.
Introduction On the Earth, biological systems are based on D-sugars and L-amino acids. The origin of biomolecular homochirality, a classical problem, has always attracted interest, and a variety of different physical and chemical phenomena have been suggested as explanations of its origin (1-3). So far, convincing theory and experiment on the origin of homochirality are still lacking (1). Norden thought that the microscopic selections are not genuine selections, because the final sense of asymmetry is determined by chance,
in other words the initial choice is random, whereas it is directed in the macroscopic selection (2). Thermodynamic and kinetic analysis shows clearly that the mechanistic selection efficiency is not of primary importance but that even very weak preference can give an amplification mechanism and complete selection in time (2,3).
Hypothesis and calculations As we know, L-amino acid peptides form righthanded or-helices, and D-ribose polynucleotides tend
Received 14 March 1997 Accepted 13 May 1997
125
126
MEDICAL HYPOTHESES
to form right-handed helices; the opposite isomers tend to form left-handed helices (4). In a-helices of L-amino acids, the incorporation of an occasional D-amino acid will be disfavored by steric hindrance and an a-helix of a racemic poly-amino acid will be significantly less stable, correspondingly, since the incorporation of L-ribose would inevitably disrupt the D-structure, the DNA helices must always contain a single form of enantiomer (2). In principle, there cannot be any energy difference between chiral helical enantiomers under achiral conditions (Fig. 1a). What is the natural macroscopic cause that gave rise to the preference of both right-handed helical nucleic acids and proteins on Earth? In the studies on the cause of physical and organic chirality, the possible importance of a 'dissymmetric universe' was first suggested by Pasteur (2,3). The solar system as a whole is asymmetric, for it is not superposable on its mirror image, and so spin and orbital rotational forces may be the cause of physical and organic chirality (3). In fact, the concepts of the protein ahelix and DNA right-handed helix were not formally pointed out until the early 1950s. Pasteur had not considered the relationships between a chiral helical force field and molecular helical enantiomers to explain the origin of biomolecular homochirality, and neither had the latter researchers, so far as we know. It is suggested here that the cause, and the origin of homochirality, may be the Earth's orbital chirality (EOC). The EOC is mainly created by two natural helical motions: both the Earth's right-handed helical rotation around its spin rotation axis and the Earth's right-handed helical revolution around the Sun. When combined with the Sun's motion in space and time, both the Earth's motions (rotation and revolution) are chiral and helical (Fig. 2) - - a fact which one often ignores! The EOC produces a net natural and macroscopic chiral right-handed helical force field over the Earth and may result in an intrinsic energy difference (AE) between helical biomolecular enantiomers (Fig. lb). At a given point on the Earth's surface, there should be an angle ((~) between the centrifugal force
of the Earth's spin rotation (Fee) and that of the Earth around the Sun (Fes). Taking into account the obliquity of the ecliptic (tp = 23.45 °) and the Earth's motion, etc. (Fig. 3b) (5), the total centrifugal force (Fete) should be given by: F¢o~= [FZee+ FZes- 2F~ F~s cos (180 ° -t~)] '~ (1) Because 0 ___t~ < 180 °, -1 < cos (180 ° - ¢)) _< 1, and the maximum Fmaxeoc= [F2ee+ F2es + 2F~ Fes]'~ = (F~ + Fes), the maximum energy difference (AEr~x) between right- and left-helical enantiomers at a point on the Earth's surface should be given by: AEmax = 2(1/2)N (Rm/COS20m)(Fee + Fe~) = N m (Rm/cOS20m)[4~2ReJ(Tee) 2 +
4x2Res/(Tes) 21
(3)
< (3.97 × 10-2) N m (Rm/COS20m) (J/molecule)
Left-handed E~e~ Right-handed enantiomers
~Oleft Left-handed enantiomers a
(4)
where N is the number of residues in a molecular helix, m is the residue's average mass (kg), R m is the radius of a molecular helix, 0m is its helical angle (Fig. 3a), and R~ and Re~ are the shortest distance from the point on the Earth's surface to the Earth's axis and the Sun, respectively; Te~ (1 day) and T~s (365 days) are the period of the Earth's rotation and revolution, respectively. When N is 1, AEm~xwould be the energy difference between either amino acid or nucleotide residue enantiomers. At a given point on the Earth's surface, according to the molecular structural parameters (Rm, 0m, m, etc.) (6) and equation (4), the AEmax between biomolecular helical enantiomers may be calculated theoretically to be in the order: BDNA > A-RNA > A-DNA >> a-protein > ~-protein. Moreover, in equation (1), as time progresses, the will make the F~oc change periodically in Tee and Te~, which may periodically change the activation energy of biomolecular reactions in living systems as well. In theory, it may be able to explain the biorhythms of biological systems on the Earth. In addition, we are interested in whether the macroscopic asymmetric helical EOC force field may affect the motion of the fundamental particles which also have an intrinsic handedness, whether there are any rela-
enantiomers
EOright
(2)
AE
T Energy
EriQht Right-handed enantiomers b
Fig. 1 The possibleenergylevelof helicalenantiomersin (a) an achiralforcefieldand (b) fight-handedhelical EOC forcefield.
127
CHIRALHELICALFORCEFIELDAND BIOMOLECULARHOMOCHIRALITY (~19.7 km/s) Sun (~35.7 kin/s) arth
Time (s)
,4 Earth Sun a
b
Fig. 2 Schematic description of the Earth's orbital chirality (EOC): (a) the Earth's circular motion around the sun; (b) the Earth's fight-handed helical revolution around the Sun. Circular motion and the right-handed helical motion of any point on the Earth's surface (except the poles) around the earth's rotation axis (not iUustrated) are similar to (a) and (b), respectively, i.e. in the figure, the label 'any point on the earth's surface' (except the poles) and 'Earth's rotation axis' could replace the labels 'Earth' and 'Sun', respectively. In consideration of all the above complex motions, the motion of any point on the earth's surface (except the poles) is a super helix in space and time.
Direction of EOC's helix axis Helix axis
Direction of the Sun's motion
l
Direction of the Earth's axis
¢p(23.45o)
\
T
(180°-~)
Sun
a
b
Fig. 3 (a) Definition of some parameters for a right-handed helix, tan 0 = P / 2 n R , for helical angle 0. V is the helical velocity of either the residue or the earth (or the point on the earth's surface, etc.) along its own helical orbit; the circular motion velocity around its helix axis is Veto= (V cos0), which produces a centripetal (or centrifugal) force in the helix: F = m (Vcm)E/R = m ( V c o s O ) 2 / R = m 4n'2R/T 2, where Tis the helical period. (b) Schematic description of the earth's obliquity (i.e. the obliquity of the ecliptic, tp = 23.45 °) and the angle (~) between F~ and F,s at a given point on the earth's surface where biomolecular helices occur at a given time (t). tionships b e t w e e n the E O C and parity-violating w e a k interaction, etc. T h e s e interesting questions h a v e b e e n studied and discussed e l s e w h e r e (7).
Experimental support As is w e l l k n o w n , under certain conditions, the l o w e r f l u o r e s c e n c e intensity o f e t h i d i u m b r o m i d e
(EB) in the presence o f D N A is, the less stable is the right-handed helical D N A - E B c o m p l e x (6,8). A s can be seen f r o m Fig. 4b, the external left-handed helical force destabilizes the right-handed helical d[G3T4G3].d[C3AaC3]-EB c o m p l e x ; then, as scanning t i m e progresses, the natural right-handed helical force field o f the E O C replaces the disappeared external left-handed helical force, resulting in increased f l u o r e s c e n c e intensity o f the right-handed helical
1 28
MEDICAL HYPOTHESES
tions, and the right-handed helical force of the EOC and the external right-handed helical force stabilizes the right-handed conformations. Therefore, the righthanded helical nucleic acid and protein enantiomers should be stabilized and selected by the natural righthanded force field of the EOC, which is the origin of homochirality on the Earth.
1 095 000
1 090 000 =.
o
1 085 000
E
,~ 1 080 000 o o 1 075 000 1 070 000
Conclusions
1 065 000
2'o
2'5
3'0
"13me (s)
Fig. 4 The time scanning curves of fluorescence intensity of DNA-EB solution at 25°C (~,= 520 nm, 2%,.= 615 nm). (a) Before helical rotation in the presence of EOC; (b) after external left-handed helical rotation (relative to the EOC's helical direction) at ~2000 r.p.m, for ~10 rain (R = 6 cm). (c) After external right-handed helical rotation [condition same as (b)]. Sample: 22.5 p2Vlbps d[G3T4Gs].d[C3A4C3]right-handed duplex in 50 mM NaAc/HAc-H20 buffer containing 45 IxM EB, pH 6.
In summary, the Earth's orbital chirality (EOC) produces an effective chiral fight-handed helical force field over the earth. It makes right-handed helical enantiomers more stable than the corresponding left-handed helical enantiomers, so terrestrial living systems must select both right-handed nucleic acids based on D-sugars and right-handed proteins based on L-amino acids.
References DNA-EB complex solution; the fluorescence intensity approaches its value before external helical rotation (Fig. 4a) after a scanning time of about 12 s. Fig. 4c shows that the external fight-handed helical force almost fails to change the fluorescence intensity of the right-handed helical DNA-EB complex, because the natural right-handed helical EOC has stabilized the latter. There are similar results from right-handed RNaseA and poly-(A).poly (U)-EB solution, and the longer helical rotation time results in larger changes of fluorescence intensity of proteins or nucleic acids-EB complex solution (data not shown). All these experimental data strongly demonstrate that the left-handed helical force destabilizes the fight-handed conforma-
1. Cohen J. Getting all turned around over the origins of life on earth. Science 1995; 267: 1265-1266. 2. Norden B. The asymmetry of life. J Mol Evol 1978; 11: 313-332. 3. Mason S F. Universal dissymmetry and the origin of biomolecular chirality. Biosystems 1987; 20: 27-35. 4. Lacey J C, Wickramasinghe W S M D, Cook G W, Anderson G. Couplings of character and of chirality in the origin of the genetic system. J Mol Evol 1993; 37: 233-239. 5. Shan Dong Science and Technology Press, eds. Handbook of Zhong Xue Xue Xi [in Chinese]. Shandong, P. R. China: Shan Dong Science and Technology Press, 1982: 260--266, 274, 281,532, 541,542. 6. Saenger W. Principles of Nucleic Acid Structure. New York: Springer-Verlag, 1984: 250, 350--353. 7. He Y J, Qi F, Qi S C. Periodicity of the earth's orbital chirality and possible mechanism of biological rhythm, submitted. 8. Scaria P V, Shafer R H. Binding of ethidium bromide to a DNA triple helix. J Biol Chem 1991; 266(9): 5417-5428.