{"id":"0aa0cda8-25a4-49f1-8baf-9ffc8f3f7d3d","arxiv_id":"2607.27495","paper_version":2,"verdict":"CONDITIONAL","confidence":"MODERATE","novelty_score":6.0,"correctness_risk":"medium","formal_verification":"none","parameter_count":5,"one_line_summary":"A switching-mobility model shows dimeric molecular motors can convert chemical free energy into directed steps through information transduction, with a predicted stall force and four measurable dwell-time distributions.","lead":"This paper builds a mathematical model of two-headed molecular motors in which only one head moves at a time, with chemical switches acting as a position sensor. It shows the motor can step forward as a \"pure information engine\" and predicts four waiting-time patterns that single-molecule experiments could measure.","discovery_kind":"new_application","skeptic_critique":{"model":"deepseek-v4-flash","headline":"Velocity formula (43) and dwell-time predictions rest on derivations confined to an unavailable Supplementary Material; without them the quantitative claims are unverifiable.","rationale":"The reader’s weakest_assumption concerns the no-energy-exchange condition for the pure-information-engine characterization. While that is a meaningful limitation for real motors, it is a modeling premise rather than an internal flaw: the model explicitly defines a motor with no landscape change upon chemical transitions, and the information-engine conclusion follows by construction. The more pressing load-bearing issue is that the quantitative predictions—especially Eq. (43), which underlies the 'reproduces experimentally observed behavior' claim—are deferred to an unavailable Supplementary Material, and the code is not actually linked. These are verifiability gaps that affect the central quantitative claims, not merely the interpretive framing. The reader’s rationale already notes these gaps, so the CONDITIONAL verdict remains appropriate: the model is plausible and internally consistent, but its quantitative claims should be paired with accessible derivations or code. No adjustment to the verdict is needed.","tokens_in":21609,"tokens_out":19074,"duration_ms":224743,"concrete_test":"Obtain the Supplementary Material and/or the GitHub code, then independently re-derive Eq. (43) from the steady-state solution of the Fokker–Planck equations (10) with the delta-function switching rates (37), without consulting the authors’ derivation. Check whether Eq. (43) follows exactly or requires an additional assumption (e.g., that the diffusive first-passage time and the residence time at the boundary are independent, or that the steady-state distribution P∞(r|ν) has a specific renewal form). If Eq. (43) cannot be reproduced without such an assumption, or if the re-derivation yields a different denominator, the central velocity formula is not established and the experimental-reproduction claim is unsupported.","verdict_should_be":"UNCHANGED","load_bearing_attack":"The paper’s quantitative core—the mean-velocity expression Eq. (43), the derived thermodynamic flows in Sec. III B, and the four dwell-time distributions in Sec. III D—is stated to be derived in SM II and SM III, but the Supplementary Material is not included in the reviewed text. Eq. (43) is the basis for the claim that the model 'reproduces experimentally observed behavior' (Sec. III A), so its correctness is load-bearing. Without the derivation, a reader cannot determine whether Eq. (43) actually follows from the Fokker–Planck system (10) with localized switching rates (37), or whether an additional approximation (e.g., a renewal assumption separating diffusive search from residence at the switching boundary) has been introduced. If such an approximation is hidden, the velocity and stall-force predictions could be quantitatively wrong even if the model is internally consistent. The code availability statement (Ref. [89]) points to a GitHub repository but gives no URL or version, so the numerical figures (Figs. 3–5, 7) cannot be reproduced independently. This gap matters because the paper’s central contribution is an analytic formula, not merely a qualitative mechanism.","agreement_with_reader":"partial"},"referee_report":{"model":"deepseek-v4-flash","summary":"This paper introduces a stochastic model of a dimeric transport motor in which two Brownian heads are alternately mobile, with a discrete chemical variable ν controlling which head moves. The switching rates are position-dependent, obey local detailed balance with an odd bias h(x0-x1), and consume chemical free energy Δμ, yet the mechanical energy landscape is unchanged upon switching. The authors change variables to relative displacement r and motor position R, derive the steady-state reduced Fokker-Planck equation for r, and use it to obtain the mean motor velocity, thermodynamic flows, and information-theoretic efficiencies. For localized switching at r=±a, they present an analytic velocity formula, stall force f_s=Δμ/(2a), and simplified thermodynamic expressions. They further coarse-grain the model to a second-order Markov dynamics and compute four dwell-time distributions. The central claim is that the motor acts as a pure information engine, with directed stepping generated by position-gated mobility switching alone.","tokens_in":21931,"tokens_out":26577,"duration_ms":265182,"significance":"The paper is conceptually valuable: it demonstrates that directed dimeric-motor stepping can arise from a minimal mobility-switching mechanism without any change in the mechanical potential, and the analytic formulas, if correct, provide a transparent connection between local detailed balance, first-passage times, and experimentally measurable dwell-time statistics. The stall-force result f_s=Δμ/(2a) and the prediction of four distinct dwell-time distributions are concrete, falsifiable signatures that distinguish the model from standard first-order chemical-kinetic descriptions. The assumptions (homodimer symmetry, localized switching, no landscape change) are stated explicitly, and the use of local detailed balance and stochastic-thermodynamics bookkeeping is a strength. However, the quantitative core—especially the mean-velocity formula (43)—is deferred to unavailable supplementary material, and there are apparent inconsistencies in the thermodynamic-flow definitions that need resolution.","major_comments":[{"comment":"The paper's quantitative core is deferred to Supplementary Material that is not included in the reviewed text. Equation (43) for the mean velocity is the basis for the claims that the model reproduces experimentally observed velocity-force behavior and for the stall force (48), but the derivation is not given in the main text. Similarly, the equivalence of Eqs. (12b) and (14) is stated to be shown in SM II, and the dwell-time distributions in Sec. III D are stated to follow from SM III. Without these derivations a reader cannot verify whether Eq. (43) follows exactly from the Fokker-Planck system (10) with localized rates (37), or whether additional approximations (e.g., renewal assumptions separating diffusive search from boundary residence) are introduced. Please include the full supplementary derivations in the review version or reproduce them in the main text.","section":"III A, Eq. (43); SM II and III"},{"comment":"There appears to be a factor-of-two inconsistency in the thermodynamic flows. From Eqs. (41)-(42), V = a(k_+ - k_-). Substituting the localized rates (37) into Eq. (22) gives W_chem = Δμ∫h(r)k(r)P∞(0,r) dr = Δμ(k_+ - k_-) = Δμ V/a, whereas Eq. (52) states W_chem = Δμ V/(2a). Similarly, Eq. (23) with the localized rates gives W_mech = -2f a(k_+ - k_-) = -2f V, whereas Eq. (24) states W_mech = -fV. These two pairs of equations cannot both be correct under the same definitions. If the flows in Eqs. (52)-(53) are defined per motor head rather than for the full dimer, that must be stated explicitly and carried through the first-law balance; if they are total flows, the factor of two changes the entropy-production rates in Eqs. (55)-(57). As written, the main-text bookkeeping is internally inconsistent.","section":"III B, Eqs. (22)-(24), (52)-(53)"},{"comment":"The claim that the motor operates as a 'pure information engine' is enforced by construction rather than derived as an emergent property. The switches do not alter the mechanical energy landscape, and the homodimer symmetry forces Ė(0)=Ė(1)=0 in Eq. (19). Thus the absence of average energy exchange between heads is a direct consequence of the model assumptions, not a generic finding about dimeric motors. The abstract and discussion present this as a general mechanism ('our findings highlight how information transduction... may underlie the remarkable performance'), which overstates the scope. I recommend adding an explicit caveat that the pure-information characterization holds only within the stated assumptions and would break if real ATP-driven conformational changes modify the potential energy landscape. This does not invalidate the model, but it is important for correct interpretatio","section":"II C, Eqs. (18)-(19); Abstract"}],"minor_comments":[{"comment":"The data-availability statement says the code is 'openly available' but Ref. [89] gives no URL, repository name, or version. The numerical figures (Figs. 3-5, 7) cannot be independently reproduced from the information provided. Please provide the actual repository link and a version identifier.","section":"Data Availability, Ref. [89]"},{"comment":"The text says the dwell-time distributions are obtained by solving a system with 'sinks,' but Eq. (68) contains source terms coupling the two chemical states at r=±a. Clarify the terminology: the sink at the leaving boundary is implemented through the absorbing condition, while the coupling terms are sources for the complementary state.","section":"III D, Eq. (68)"},{"comment":"The sentence 'since two successive head transitions are involved in a full motor step' should be unpacked. As written it is not immediately clear why the flux ratio (75) equals e^{2βΔF} rather than e^{βΔF}; a short derivation or a precise definition of 'full motor step' in this context would help.","section":"III D, Eq. (75)"},{"comment":"There are several wording/grammar issues, e.g., 'η_TD of 0.4−0.6 have been reported' should be 'values of η_TD... have been reported'; 'sigma' appears instead of σ in the paragraph after Eq. (70); and the notation D∂²_{rR}P in Eqs. (8) is nonstandard and should be defined as ∂_r∂_R.","section":"Throughout"}],"recommendation":"major_revision","confidential_remarks":"The central idea is appealing and the main-text setup is mostly clear, but the manuscript as submitted cannot be accepted because the derivations behind Eq. (43) and the dwell-time results are in a supplementary file that was not provided, and the thermodynamic-flow expressions in Sec. III B appear to have a factor-of-two inconsistency. If the supplementary material resolves these points and the factor issue is simply a matter of per-head versus total flows, I would be supportive. The 'pure information engine' framing should also be toned down or explicitly qualified, since it is a consequence of the model assumptions rather than an independent discovery."},"author_rebuttal":null,"desk_editor":{"model":"deepseek-v4-flash","letter":"Colleague, here's the take on 2607.27495.\n\nThe paper's real contribution is a clean model: two overdamped Brownian heads, one mobile at a time, with position-dependent switching rates that obey local detailed balance. For localized switching at ±a it derives an analytic mean velocity and a stall force fs = Δμ/(2a), plus four dwell-time distributions arising from a second-order Markov coarse-graining. That is genuinely new for dimeric motors and directly testable on single-molecule trajectories. The main-text derivation is self-consistent, and the homodimer symmetry argument that no net energy flows between heads is correct.\n\nThe soft spots are real. First, the quantitative core—Eq. (43) and all the dwell-time distributions—is supposedly derived in a Supplementary Material that was not part of the manuscript I read. The velocity formula is load-bearing for the claim that the model 'reproduces experimentally observed behavior,' and without the derivation I cannot rule out a hidden approximation (e.g., a renewal assumption separating diffusive search from residence). This is the biggest issue and it is easily fixed by moving the SM into the paper or providing a clear derivation.\n\nSecond, the 'pure information engine' conclusion is largely true by construction. The authors assume switches do not change the energy landscape, and homodimer symmetry forbids average energy exchange. That is not a flaw in the model, but it means the information-engine framing is an interpretation rather than a derived result. The paper should say that more plainly.\n\nThird, the experimental-reproduction claim is backed by no data overlay. Figures 3–4 show velocity curves that look qualitatively like kinesin data, but there is no quantitative comparison. The claim should be downgraded to 'consistent with the observed linear force-velocity relation near stall.'\n\nFourth, the model is heavily idealized—constant load, no stochastic detachment, switching strictly localized at ±a. The authors mention some of these in the Discussion, but they don't address how the dwell-time predictions would be affected by a realistic linker or finite-width switching zones.\n\nThe citation pattern is fine; the group is building on its own bipartite information-engine papers, and that is legitimate when the cited results are relevant. The stated code availability has no URL, which matters since the figures are otherwise unreproducible.\n\nWho should read this: stochastic thermodynamics people and experimentalists interested in dwell-time analysis of kinesin/myosin. I'd bring it to reading group, and a good referee should see it—but only with the Supplementary Material included and the claims tempered. Verdict: major revision.","headline":"New switching-mobility model for dimeric motors with testable dwell-time predictions, but the load-bearing derivations sit in an inaccessible Supplementary Material.","tokens_in":22362,"tokens_out":2362,"would_cite":false,"duration_ms":25170,"reading_group":"maybe","serious_thinker":"yes","would_accept_peer_review":true},"rs_alignment":null,"lean_confirmation":null,"pith_extraction":{"msc":[],"pacs":["87.16.Nn"],"model":"deepseek-v4-flash","headline":"A dimeric transport motor can step as a pure information engine, with position-gated mobility switching alone producing directed motion and the observed stall force.","keywords":["molecular motors","information engines","Maxwell demon","stochastic thermodynamics","dimeric motors","dwell-time distributions","stall force","Brownian ratchet"],"falsifier":"Measure the mechanical work done on a motor head during a single chemical transition (e.g., by high-resolution optical trapping with fast force feedback synchronized to ATP binding). If the chemical step injects a nonzero average energy into the mechanical coordinate—beyond the energy of the diffusive search—the zero-energy-exchange core of the model is falsified. Alternatively, measure dwell times conditioned on the previous binding site: if the four predicted distributions collapse to two, the second-order Markov structure is absent.","tokens_in":21469,"feed_emoji":"🧬","tokens_out":4859,"duration_ms":49621,"temperature":0.7,"pith_summary":"The paper proposes that a two-headed transport motor can generate directed stepping without any of the usual energy exchange between its chemical and mechanical parts. In the model, the two heads are Brownian particles that take turns moving: a chemical state flips which head is mobile, and the flip rates depend on the heads' relative position and on the ATP-derived chemical free energy. Because the switch never changes the mechanical energy landscape, the motor transduces only information between the chemical and mechanical subsystems—it operates as an autonomous Maxwell demon. For switches localized at discrete binding sites, the model yields a closed-form mean velocity that reproduces experimental force-velocity curves and the stall force f_s = Δμ/(2a) characteristic of tightly coupled motors. It also predicts that coarse-grained stepping is a second-order Markov process, giving four distinct dwell-time distributions testable in single-molecule experiments.","feed_headline":"Model drives dimeric motors on information alone","feed_subtitle":"Switching which head moves, gated by position, yields the stall force with no energy exchange.","key_machinery":"The load-bearing object is a pair of overdamped Langevin equations for the head coordinates x0, x1, controlled by a two-state chemical variable ν that sets each head's mobility to zero or the diffusion constant D. Switching rates k(r) = Γ(r) exp(±βΔμ h(r)/2) depend on the relative displacement r = x0 - x1 and satisfy local detailed balance. Homodimer symmetry (identical heads, rates invariant under exchanging them) forces the steady-state energy flow between heads to vanish. For analytical results the switching is localized at r = ±a, so the entire steady state collapses to two effective rates k± for forward/backward switches; the mean velocity is then expressed through diffusive first-passa","core_discovery":"The central claim is that directed motion of a dimeric transport motor can arise solely from position-gated mobility switching. At any instant exactly one head is mobile; the other is fixed to the filament. The mobile head diffuses in the symmetric linker potential plus a constant load, and when it reaches a target displacement the chemical state flips, swapping which head moves. The flipping rates obey local detailed balance with an odd, saturating function of the head separation, so forward flips are favored whenever the moving head is ahead. Because the chemical switch does not alter the potential, the average energy flow between chemical and mechanical degrees of freedom is zero at stead","pith_inferences":["Editorial inference: if the pure-information picture holds, a practical design principle for synthetic nanomotors would be to engineer position-sensing gates rather than strained conformational transitions, and ATP consumption would primarily pay for the gating decision.","Editorial inference: the four dwell-time distributions provide a sharp discriminator: re-analyzing existing single-molecule trajectory data conditioned on the previous binding site could test the model without new experiments, since standard kinetic analyses that report only two distributions would miss the second-order memory.","Editorial inference: for heterodimeric or inchworm motors, the zero-energy-exchange premise breaks, so the model predicts deviations from f_s = Δμ/(2a); measuring stall forces across motor families could map where information transduction dominates and where it does not.","Editorial inference: the mechanism offers an autonomous realization of the feedback used in non-autonomous information engines, so the formalism may extend to other processive molecular machines that step along a track."],"forward_implications":["If the model is right, kinesin- and myosin-family motors need not use conformational free-energy changes to bias stepping; position-dependent gating of head mobility alone can produce directed motion.","The stall force f_s = Δμ/(2a) and the linear efficiency η = f/f_s follow from tight coupling, matching the experimentally observed linear force-velocity relation near stall.","The velocity formula predicts saturation at V_max = a/τ_diff, set by the mechanics of diffusing between binding sites, so chemical driving beyond a point cannot speed the motor.","Coarse-grained motor stepping is second-order Markovian: four dwell-time distributions (forward/backward from two initial chemical states) should be visible in single-molecule trajectories.","The subsystem efficiencies η_chem and η_mech frame the motor's performance as information transduction, so experiments measuring work and heat flows can test the information-engine interpretation."],"fun_headline_variants":["Motors step on pure information, not energy","Position-gated stepping: Maxwell demon in motors","Pure info engine: dimer motor walks without energy","No energy, just information: how dimer motors step","Dimeric motor runs on information, zero energy"],"cache_read_input_tokens":2304,"weakest_assumption_plain":"The load-bearing premise is that a chemical switch changes only which head is mobile, never the mechanical energy landscape; if real ATP-driven transitions do conformational work on the heads or alter the linker potential, the 'pure information engine' characterization fails, even if the velocity and stall-force formulas remain approximate.","fun_headline_variants_meta":{"raw":{"variants":["Motors step on pure information, not energy","Position-gated stepping: Maxwell demon in motors","Pure info engine: dimer motor walks without energy","No energy, just information: how dimer motors step","Dimeric motor runs on information, zero energy"]},"model":"deepseek-v4-flash","effort":"low","cost_usd":0.000347,"raw_usage":{"total_tokens":1714,"prompt_tokens":696,"completion_tokens":1018,"prompt_tokens_details":{"cached_tokens":256},"prompt_cache_hit_tokens":256,"prompt_cache_miss_tokens":440,"completion_tokens_details":{"reasoning_tokens":946}},"tokens_in":440,"tokens_out":1018,"duration_ms":28872,"temperature":1.0,"reasoning_tokens":946,"cache_read_input_tokens":256,"cache_creation_input_tokens":0},"cache_creation_input_tokens":0},"created_at":"2026-08-04T01:21:26.033768+00:00","model_set":{"reader":"deepseek-v4-flash"},"falsifier":"Measure the mechanical work done on a motor head during a single chemical transition (e.g., by high-resolution optical trapping with fast force feedback synchronized to ATP binding). If the chemical step injects a nonzero average energy into the mechanical coordinate—beyond the energy of the diffusive search—the zero-energy-exchange core of the model is falsified. Alternatively, measure dwell times conditioned on the previous binding site: if the four predicted distributions collapse to two, the second-order Markov structure is absent.","supporting_citations":[],"review_version":2}