arXiv subjects

Debashish Chowdhury

Publications and source records attributed to Debashish Chowdhury.

At least 55 records · Page 3Linked to original sources

arXiv2012

Template-directed biopolymerization: tape-copying Turing machines

DNA, RNA and proteins are among the most important macromolecules in a living cell. These molecules are polymerized by molecular machines. These natural nano-machines polymerize such macromolecules, adding one monomer at a time, using another linear polymer as the corresponding template. The machine utilizes input chemical energy to move along the template which also serves as a track for the movements of the machine. In the Alan Turing year 2012, it is worth pointing out that these machines are "tape-copying Turing machines". We review the operational mechanisms of the polymerizer machines and their collective behavior from the perspective of statistical physics, emphasizing their common features in spite of the crucial differences in their biological functions. We also draw attention of the physics community to another class of modular machines that carry out a different type of template-directed polymerization. We hope this review will inspire new kinetic models for these modular machines.

physics.bio-ph↗

arXiv2012

Error correction during DNA replication

DNA polymerase (DNAP) is a dual-purpose enzyme that plays two opposite roles in two different situations during DNA replication. It plays its normal role as a {\it polymerase} catalyzing the elongation of a new DNA molecule by adding a monomer. However, it can switch to the role of an {\it exonuclease} and shorten the same DNA by cleavage of the last incorporated monomer from the nascent DNA. Just as misincorporated nucleotides can escape exonuclease causing replication error, correct nucleotide may get sacrificed unnecessarily by erroneous cleavage. The interplay of polymerase and exonuclease activities of a DNAP is explored here by developing a minimal stochastic kinetic model of DNA replication. Exact analytical expressions are derived for a few key statistical distributions; these characterize the temporal patterns in the mechanical stepping and the chemical (cleavage) reaction. The Michaelis-Menten-like analytical expression derived for the average rates of these two processes not only demonstrate the effects of their coupling, but are also utilized to measure the extent of {\it replication error} and {\it erroneous cleavage}.

physics.bio-ph↗

arXiv2012

Machines of life: catalogue, stochastic process modeling, probabilistic reverse engineering and the PIs- from Aristotle to Alberts

Molecular machines consist of either a single protein or a macromolecular complex composed of protein and RNA molecules. Just like their macroscopic counterparts, each of these nano-machines has an engine that "transduces" input energy into an output form which is then utilized by its coupling to a transmission system for appropriate operations. The theory of heat engines, pioneered by Carnot, rests on the second law of equilibrium thermodynamics. However, the engines of molecular machines, operate under isothermal conditions far from thermodynamic equilibrium. Moreover, one of the possible mechanisms of energy transduction, popularized by Feynman and called Brownian ratchet, does not even have any macroscopic counterpart. But, {\it molecular machine is not synonymous with Brownian ratchet}; a large number of molecular machines actually execute a noisy power stroke, rather than operating as Brownian ratchet. The man-machine analogy, a topic of intense philosophical debate in which many leading philosophers like Aristotle and Descartes participated, was extended to similar analogies at the cellular and subcellular levels after the invention of optical microscope. The idea of molecular machine, pioneered by Marcelo Malpighi, has been pursued vigorously in the last fifty years. It has become a well established topic of current interdisciplinary research as evident from the publication of a very influential paper by Alberts towards the end of the twentieth century. Here we give a non-technical overview of the strategies for (a) stochastic modeling of mechano-chemical kinetic processes, and (b) model selection based on statistical inference drawn from analysis of experimental data. It is written for non-experts and from a broad perspective, showing overlapping concepts from several different branches of physics and from other areas of science and technology.

physics.bio-ph↗

arXiv2012

Footprint traversal by ATP-dependent chromatin remodeler motor

ATP-dependent chromatin remodeling enzymes (CRE) are bio-molecular motors in eukaryotic cells. These are driven by a chemical fuel, namely, adenosine triphosphate (ATP). CREs actively participate in many cellular processes that require accessibility of specific segments of DNA which are packaged as chromatin. The basic unit of chromatin is a nucleosome where 146 bp $\sim$ 50 nm of a double stranded DNA (dsDNA) is wrapped around a spool formed by histone proteins. The helical path of histone-DNA contact on a nucleosome is also called "footprint". We investigate the mechanism of footprint traversal by a CRE that translocates along the dsDNA. Our two-state model of a CRE captures effectively two distinct chemical (or conformational) states in the mechano-chemical cycle of each ATP-dependent CRE. We calculate the mean time of traversal. Our predictions on the ATP-dependence of the mean traversal time can be tested by carrying out {\it in-vitro} experiments on mono-nucleosomes.

physics.bio-ph↗

arXiv2011

Stochastic theory of protein synthesis and polysome: ribosome profile on a single mRNA transcript

The process of polymerizing a protein by a ribosome, using a messenger RNA (mRNA) as the corresponding template, is called {\it translation}. Ribosome may be regarded as a molecular motor for which the mRNA template serves also as the track. Often several ribosomes may translate the same (mRNA) simultaneously. The ribosomes bound simultaneously to a single mRNA transcript are the members of a polyribosome (or, simply, {\it polysome}). Experimentally measured {\it polysome profile} gives the distribution of polysome {\it sizes}. Recently a breakthrough in determining the instantaneous {\it positions} of the ribosomes on a given mRNA track has been achieved and the technique is called {\it ribosome profiling} \cite{ingolia10,guo10}. Motivated by the success of these techniques, we have studied the spatio-temporal organization of ribosomes by extending a theoretical model that we have reported elsewhere \cite{sharma11}. This extended version of our model incorporates not only (i) mechano-chemical cycle of individual ribomes, and (ii) their steric interactions, but also (iii) the effects of (a) kinetic proofreading, (b) translational infidelity, (c) ribosome recycling, and (d) sequence inhomogeneities. The theoretical framework developed here will serve in guiding further experiments and in analyzing the data to gain deep insight into various kinetic processes involved in translation.

physics.bio-ph↗

arXiv2011

Stochastic kinetics of a single headed motor protein: dwell time distribution of KIF1A

KIF1A, a processive single headed kinesin superfamily motor, hydrolyzes Adenosine triphosphate (ATP) to move along a filamentous track called microtubule. The stochastic movement of KIF1A on the track is characterized by an alternating sequence of pause and translocation. The sum of the durations of pause and the following translocation defines the dwell time. Using the NOSC model (Nishinari et. al. PRL, {\bf 95}, 118101 (2005)) of individual KIF1A, we systematically derive an analytical expression for the dwell time distribution. More detailed information is contained in the probability densities of the "conditional dwell times" $τ_{\pm\pm}$ in between two consecutive steps each of which could be forward (+) or backward (-). We calculate the probability densities $Ξ_{\pm\pm}$ of these four conditional dwell times. However, for the convenience of comparison with experimental data, we also present the two distributions $Ξ_{\pm}^{*}$ of the times of dwell before a forward (+) and a backward (-) step. In principle, our theoretical prediction can be tested by carrying out single-molecule experiments with adequate spatio-temporal resolution.

physics.bio-ph↗

arXiv2011

Distribution of dwell times of a ribosome: effects of infidelity, kinetic proofreading and ribosome crowding

Ribosome is a molecular machine that polymerizes a protein where the sequence of the amino acid residues, the monomers of the protein, is dictated by the sequence of codons (triplets of nucleotides) on a messenger RNA (mRNA) that serves as the template. The ribosome is a molecular motor that utilizes the template mRNA strand also as the track. Thus, in each step the ribosome moves forward by one codon and, simultaneously, elongates the protein by one amino acid. We present a theoretical model that captures most of the main steps in the mechano-chemical cycle of a ribosome. The stochastic movement of the ribosome consists of an alternating sequence of pause and translocation; the sum of the durations of a pause and the following translocation is the time of dwell of the ribosome at the corresponding codon. We derive the analytical expression for the distribution of the dwell times of a ribosome in our model. Whereever experimental data are available, our theoretical predictions are consistent with those results. We suggest appropriate experiments to test the new predictions of our model, particularly, the effects of the quality control mechanism of the ribosome and that of their crowding on the mRNA track.

physics.bio-ph↗

arXiv2010

Quality control by a mobile molecular workshop: quality versus quantity

Ribosome is a molecular machine that moves on a mRNA track while, simultaneously, polymerizing a protein using the mRNA also as the corresponding template. We define, and analytically calculate, two different measures of the efficiency of this machine. However, we arugue that its performance is evaluated better in terms of the translational fidelity and the speed with which it polymerizes a protein. We define both these quantities and calculate these analytically. Fidelity is a measure of the quality of the products while the total quantity of products synthesized in a given interval depends on the speed of polymerization. We show that for synthesizing a large quantity of proteins, it is not necessary to sacrifice the quality. We also explore the effects of the quality control mechanism on the strength of mechano-chemical coupling. We suggest experiments for testing some of the ideas presented here.

physics.bio-ph↗

arXiv2009

Stochastic kinetics of ribosomes: single motor properties and collective behavior

Synthesis of protein molecules in a cell are carried out by ribosomes. A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an {\it exact} analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a ``Michaelis-Menten-like'' equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechano-chemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes simultaneously move on the same mRNA track, while each synthesizes a copy of the same protein. We extend the model of a single ribosome by incorporating steric exclusion of different individuals on the same track. We draw the phase diagram of this model of ribosome traffic in 3-dimensional spaces spanned by experimentally controllable parameters. We suggest new experimental tests of our theoretical predictions.

physics.bio-ph↗

arXiv2009

RNA polymerase motor on DNA track: effects of interactions, external force and torque

RNA polymerase (RNAP) is a mobile molecular workshop that polymerizes a RNA molecule by adding monomeric subunits one by one, while moving step by step on the DNA template itself. Here we develop a theoretical model by incorporating the steric interactions of the RNAPs and their mechanochemical cycles which explicitly captures the cyclical shape changes of each motor. Using this model, we explain not only the dependence of the average velocity of a RNAP on the externally applied load force, but also predict a {\it nonmotonic} variation of the average velocity on external torque. We also show the effect of steric interactions of the motors on the total rate of RNA synthesis. In principle, our predictions can be tested by carrying out {\it in-vitro} experiments which we suggest here.

physics.bio-ph↗

arXiv2009

RNA polymerase motors: dwell time distribution, velocity and dynamical phases

Polymerization of RNA from a template DNA is carried out by a molecular machine called RNA polymerase (RNAP). It also uses the template as a track on which it moves as a motor utilizing chemical energy input. The time it spends at each successive monomer of DNA is random; we derive the exact distribution of these "dwell times" in our model. The inverse of the mean dwell time satisfies a Michaelis-Menten-like equation and is also consistent with a general formula derived earlier by Fisher and Kolomeisky for molecular motors with unbranched mechano-chemical cycles. Often many RNAP motors move simultaneously on the same track. Incorporating the steric interactions among the RNAPs in our model, we also plot the three-dimensional phase diagram of our model for RNAP traffic using an extremum current hypothesis.

cond-mat.stat-mech↗

arXiv2009

Trafficlike collective movement of ants on trails: absence of jammed phase

We report experimental results on unidirectional traffic-like collective movement of ants on trails. Our work is primarily motivated by fundamental questions on the collective spatio-temporal organization in systems of interacting motile constituents driven far from equilibrium. Making use of the analogies with vehicular traffic, we analyze our experimental data for the spatio-temporal organisation of the ants on the trail. From this analysis, we extract the flow-density relation as well as the distributions of velocities of the ants and distance-headways. Some of our observations are consistent with our earlier models of ant-traffic, which are appropriate extensions of the asymmetric simple exclusion process (ASEP). In sharp contrast to highway traffic and most other transport processes, the average velocity of the ants is almost independent of their density on the trail. Consequently, no jammed phase is observed.

physics.bio-ph↗

arXiv2009

Characteristics of ant-inspired traffic flow: Applying the social insect metaphor to traffic models

We investigate the organization of traffic flow on preexisting uni- and bidirectional ant trails. Our investigations comprise a theoretical as well as an empirical part. We propose minimal models of uni- and bi-directional traffic flow implemented as cellular automata. Using these models, the spatio-temporal organization of ants on the trail is studied. Based on this, some unusual flow characteristics which differ from those known from other traffic systems, like vehicular traffic or pedestrians dynamics, are found. The theoretical investigations are supplemented by an empirical study of bidirectional traffic on a trail of Leptogenys processionalis. Finally, we discuss some plausible implications of our observations from the perspective of flow optimization.

stat.AP↗

arXiv2008

Transcriptional bursts: a unified model of machines and mechanisms

{\it Transcription} is the process whereby RNA molecules are polymerized by molecular machines, called RNA polymerase (RNAP), using the corresponding DNA as the template. Recent {\it in-vivo} experiments with single cells have established that transcription takes place in "bursts" or "pulses". In this letter we present a model that captures not only the mechano-chemistry of individual RNAPs and their steric interactions but also the switching of the gene between the ON and OFF states. This model accounts for the statistical properties of the transcriptional bursts. It also shows how the quantitative features of the distributions of these bursts can be tuned by controlling the appropriate steps of operation of the RNAP machines.

physics.bio-ph↗

arXiv2008

Resource Letter: Bio-molecular Nano-machines: where Physics, Chemistry, Biology and Technology meet

Cell is the structural and functional unit of life. This Resource Letter serves as a guide to the literature on nano-machines which drive not only intracellular movements, but also motility of the cell. These machines are usually proteins or macromolecular assemblies which require appropriate fuel for their operations. Although, traditionally, these machines were subjects of investigation in biology and biochemistry, increasing use of the concepts and techniques of physics in recent years have contributed to the quantitative understanding of the fundamental principles underlying their operational mechanisms. The possibility of exploiting these principles for the design and control of artificial nano-machines has opened up a new frontier in the bottom-up approach to nano-technology.

physics.bio-ph↗

arXiv2008

Length control of microtubules by depolymerizing motor proteins

In many intracellular processes, the length distribution of microtubules is controlled by depolymerizing motor proteins. Experiments have shown that, following non-specific binding to the surface of a microtubule, depolymerizers are transported to the microtubule tip(s) by diffusion or directed walk and, then, depolymerize the microtubule from the tip(s) after accumulating there. We develop a quantitative model to study the depolymerizing action of such a generic motor protein, and its possible effects on the length distribution of microtubules. We show that, when the motor protein concentration in solution exceeds a critical value, a steady state is reached where the length distribution is, in general, non-monotonic with a single peak. However, for highly processive motors and large motor densities, this distribution effectively becomes an exponential decay. Our findings suggest that such motor proteins may be selectively used by the cell to ensure precise control of MT lengths. The model is also used to analyze experimental observations of motor-induced depolymerization.

physics.bio-ph↗

arXiv2008

Fluctuations in protein synthesis from a single RNA template: stochastic kinetics of ribosomes

Proteins are polymerized by cyclic machines called ribosome which use their messenger RNA (mRNA) track also as the corresponding template and the process is called translation. We explore, in depth and detail, the stochastic nature of the translation. We compute various distributions associated with the translation process; one of them, namely dwell time distribution, has been measured in recent single ribosome experiments (Wen et al. Nature {\bf 452}, 598 (2008)). The form of this distribution predicted by our theory is consistent with that extracted from the experimental data. For our quantitative calculations, we use a model that captures both the mechano-chemistry of each individual ribosome as well as their steric interactions. We also demonstrate the effects of the sequence inhomogeneities of real genes on the fluctuations and noise in translation. In principle, our new predictions can be tested by carrying out {\it in-vitro} experiments.

physics.bio-ph↗

arXiv2008

A two-state model for helicase translocation and unwinding of nucleic acids

Helicases are molecular motors that unwind double-stranded nucleic acids (dsNA), such as DNA and RNA). Typically a helicase translocates along one of the NA single strands while unwinding and uses adenosine triphosphate (ATP) hydrolysis as an energy source. Here we model of a helicase motor that can switch between two states, which could represent two different points in the ATP hydrolysis cycle. Our model is an extension of the earlier Betterton-Jülicher model of helicases to incorporate switching between two states. The main predictions of the model are the speed of unwinding of the dsNA and fluctuations around the average unwinding velocity. Motivated by a recent claim that the NS3 helicase of Hepatitis C virus follows a flashing ratchet mechanism, we have compared the experimental results for the NS3 helicase with a special limit of our model which corresponds to the flashing ratchet scenario. Our model accounts for one key feature of the experimental data on NS3 helicase. However, contradictory observations in experiments carried out under different conditions limit the ability to compare the model to experiments.

physics.bio-ph↗