Molecular Ratchets Research Articles

Molecular motors and nonuniform ratchets.

Dimeric kinesin presumably moves in a "hand-over-hand" fashion via alternating steps of its two heads, which can cooperate in various ways. This motion is discussed in the framework of nonuniform ratchet models in which the molecular motor is described by M internal states and undergoes transitions at K spatial locations within the period of the molecular force potentials. Two subclasses of models with (M, K)=(3, 2) and (M, K)=(2, 2) are studied which correspond to weakly and strongly cooperative heads, respectively. Both subclasses lead to the same universal relationship between the motor velocity and the unbinding rate constant of the motor heads which is reminiscent of, but distinct from, Michaelis-Menten kinetics.

Electrophoresis of DNA and other polyelectrolytes: Physical mechanisms

The dramatic recent advances in molecular biology, which have opened a new era in medicine and biotechnology, rely on improved techniques to study large molecules. Electrophoresis is one of the most important of these. Separation of DNA by size, in particular, is at the heart of genome mapping and sequencing and is likely to play an increasing role in diagnosis. This article reviews, from the point of view of a physicist, the mechanisms responsible for electrophoretic separation of polyelectrolytes. This separation is mainly performed in gels, and a wide variety of migration mechanisms can come into play, depending on the polyelectrolyte's architecture, on the electric fields applied, and on the properties of the gel. After a brief review of the thermodynamic and electrohydrodynamic principles relating to polyelectrolyte solutions, the author treats the phenomenology of electrophoresis and describes the conceptual and theoretical tools in the field. The reptation mechanisms, by which large flexible polyelectrolytes thread their way through the pores of the gel matrix, play a prominent role. Biased reptation, the extension of this model to electrophoresis, provides a very intuitive framework within which numerous physical ideas can be introduced and discussed. It has been the most popular theory in this domain, and it remains an inspiring concept for current development. There have also been important advances in experimental techniques such as single-molecule viodeomicroscopy and the development of nongel separation media and mechanisms. These, in turn, form the basis for fast-developing and innovative technologies like capillary electrophoresis, electrophoresis on microchips, and molecular ratchets.

Molecular ratchets: verification of the principle of detailed balance and the second law of dynamics

We argue that the recent experiments of Kelly et al. [Angew. Chem. Int. Ed. Engl. 36, 1866 (1997)] on molecular ratchets, in addition to being in agreement with the second law of thermodynamics, is a test of the principle of detailed balance for the ratchet. We suggest experiments, using an asymmetric ratchet, to further test the principle. We also point out methods involving a time variation of the temperature to give it a directional motion.

Chiral dissociation dynamics of molecular ratchets: Preferential senses of rotary motion in microscopic systems

Classical trajectory calculations are used to study the origin of chiral dynamics in the dissociation of structurally chiral molecules. A ratchet torsional potential about the chemical bond to be broken produces a net preference for one sense of product rotation about the recoil velocity vector. The dynamical chirality of these helical product trajectories is quantified using body-fixed bipolar moments that can be measured in gas-phase-photodissociation experiments. It is shown that the chiral dynamics is generated in the exit channel as the dissociation dynamics becomes irreversible, and is greatly accentuated by a late barrier to the dissociation reaction.

In Search of Molecular Ratchets

Triptycylhelicenes 1 and 2 were examined as molecular rachets (see picture) in which the triptycene serves as the rachet wheel (a) and the helicenes as pawl (b) and spring (c). The ease of rotation of the triptycene wheel depends on the helicene springs and pawls, but do these have any influence on the direction of rotation?

Bisaldehyde allosteric effectors as molecular ratchets and probes.

Four new series of monoaldehyde bisacids and bisaldehyde bisacids with varying chain lengths have been synthesized and evaluated as allosteric effectors of hemoglobin. Molecular modeling, oxygen equilibrium, and crystallographic studies were combined for structure/function studies. Crystallographic analyses of the bisaldehydes reveal that Schiff base interaction occurred exclusively between Val 1 alpha and Lys 99 alpha of the opposite alpha chain even though the two terminal Val 1 alpha nitrogens are ideally spaced to also form cross-links. The reason for the observed mode of binding appears to be the influence of chain direction set by key substitutions on the bisaldehyde molecule. Even longer chain derivatives that could overcome the direction set by the key functional groups bind in the same manner. These studies support the general conclusion that long flexible molecules prefer to bind along cavity walls, like double-sided molecular sticky tape, rather than span large open spaces with few chances for interaction. The cross-linked bisaldehydes bind at the same site when incubated under both allosteric states and exhibit reduced cooperativity with a significant decrease in oxygen affinity. The chain length acts as a molecular ratchet and dictates the degree of allosteric effect observed. The tighter the cross-link, the greater the constraint on the tense- (T-) state and the stronger the allosteric effect that is produced. The monoaldehyde bisacids bind in the same fashion with Schiff base formation at Val 1 alpha while the acid that replaces the second aldehyde moiety forms a salt bridge with Lys 99 alpha of the opposite subunit. This class of molecules has weaker allosteric effector activity as would be expected with replacement of one covalent bond by a salt bridge. The importance of Lys 99 alpha on the allosteric equilibrium is confirmed.