arXiv subjects

José N. Onuchic

Publications and source records attributed to José N. Onuchic.

12 recordsLinked to original sources

arXiv2025

Quantum Simulation of Charge and Exciton Transfer in Multi-mode Models using Engineered Reservoirs

Quantum simulation offers a route to study open-system molecular dynamics in non-perturbative regimes by programming the interactions among electronic, vibrational, and environmental degrees of freedom on similar energy scales. Trapped-ion systems possess this capability, with their native spins, phonons, and tunable dissipation integrated within a single platform. Here, we demonstrate an open-system quantum simulation of charge and exciton transfer in a multi-mode linear vibronic coupling model. Employing tailored spin-phonon interactions alongside reservoir engineering techniques, we emulate a system with two dissipative vibrational modes coupled to donor and acceptor electronic sites and follow its non-equilibrium dynamics. We continuously tune the system from the charge transfer (CT) regime to the vibrationally assisted exciton transfer (VAET) regime by controlling the vibronic coupling strengths. We find that degenerate modes enhance CT and VAET rates at large energy gaps, while non-degenerate modes activate slow-mode pathways that reduce the energy-gap dependence, thus enlarging the window for efficient transfer. These results show that the presence of one additional vibration introduces interfering vibrationally assisted pathways and reshapes non-perturbative quantum excitation transfer. Our work establishes a scalable and hardware-efficient route to simulating chemically relevant, many-mode vibronic processes with engineered environments, guiding the design of next-generation organic photovoltaics and molecular electronics.

quant-ph↗

arXiv2025

The need to implement FAIR principles in biomolecular simulations

This letter illustrates the opinion of the molecular dynamics (MD) community on the need to adopt a new FAIR paradigm for the use of molecular simulations. It highlights the necessity of a collaborative effort to create, establish, and sustain a database that allows findability, accessibility, interoperability, and reusability of molecular dynamics simulation data. Such a development would democratize the field and significantly improve the impact of MD simulations on life science research. This will transform our working paradigm, pushing the field to a new frontier. We invite you to support our initiative at the MDDB community (https://mddbr.eu/community/) Now published as: Amaro, R.E., et al. The need to implement FAIR principles in biomolecular simulations. Nat Methods (2025) https://doi.org/10.1038/s41592-025-02635-0

q-bio.BM↗

arXiv2025

Trapped-Ion Quantum Simulation of Electron Transfer Models with Tunable Dissipation

Electron transfer is at the heart of many fundamental physical, chemical, and biochemical processes essential for life. The exact simulation of these reactions is often hindered by the large number of degrees of freedom and by the essential role of quantum effects. Here, we experimentally simulate a paradigmatic model of molecular electron transfer using a multispecies trapped-ion crystal, where the donor-acceptor gap, the electronic and vibronic couplings, and the bath relaxation dynamics can all be controlled independently. By manipulating both the ground-state and optical qubits, we observe the real-time dynamics of the spin excitation, measuring the transfer rate in several regimes of adiabaticity and relaxation dynamics. Our results provide a testing ground for increasingly rich models of molecular excitation transfer processes that are relevant for molecular electronics and light-harvesting systems.

quant-ph↗

arXiv2022

Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway

The Notch-Delta signaling pathway mediates cell differentiation implicated in many regulatory processes including spatiotemporal patterning in tissues by promoting alternate cell fates between neighboring cells. At the multicellular level, this "lateral inhibition" principle leads to checkerboard patterns of Sender and Receiver cells. While it is well known that stochasticity modulates cell fate specification, little is known about how stochastic fluctuations at the cellular level propagate during multicell pattern formation. Here, we model stochastic fluctuations in the Notch-Delta pathway in the presence of two different noise types - shot and white - for a multicell system. The results show that intermediate fluctuations reduce disorder and guide the multicell lattice toward more checkerboard like patterns. By further analyzing cell fate transition events, we demonstrate that intermediate noise amplitudes provide enough perturbation to facilitate "proofreading" of disordered patterns and cause cells to switch to their correct ordered state. Conversely, high noise can override environmental signals coming from neighboring cells and lead to switching between ordered and disordered patterns. Therefore, in analogy with spin glass systems, intermediate noise levels allow the multicell Notch system to escape frustrated patterns and relax towards the lower energy checkerboard pattern while at large noise levels the system is unable to find this ordered base of attraction.

q-bio.CB↗

arXiv2021

Contact map dependence of a T cell receptor binding repertoire

The T cell arm of the adaptive immune system provides the host protection against unknown pathogens by discriminating between host and foreign material. This discriminatory capability is achieved by the creation of a repertoire of cells each carrying a T cell receptor (TCR) specific to non-self antigens displayed as peptides bound to the major histocompatibility complex (pMHC). The understanding of the dynamics of the adaptive immune system at a repertoire level is complex, due to both the nuanced interaction of a TCR-pMHC pair and to the number of different possible TCR-pMHC pairings, making computationally exact solutions currently unfeasible. To gain some insight into this problem, we study an affinity-based model for TCR-pMHC binding in which a crystal structure is used to generate a distance-based contact map that weights the pairwise amino acid interactions. We find that the TCR-pMHC binding energy distribution strongly depends both on the number of contacts and the repeat structure allowed by the topology of the contact map of choice; this in turn influences T cell recognition probability during negative selection, with higher variances leading to higher survival probabilities. In addition, we quantify the degree to which neoantigens with mutations in sites with higher contacts are recognized at a higher rate.

physics.bio-ph↗

arXiv2017

Distinguishing Mechanisms Underlying EMT Tristability

Background: The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models - ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done. Results: Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E-E/M-M, the different responses of SNAIL and ZEB1 to exogenous TGF-b and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2. Conclusions: These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes.

q-bio.CB↗

arXiv2011

A structural perspective on the dynamics of kinesin motors

Despite significant fluctuation under thermal noise, biological machines in cells perform their tasks with exquisite precision. Using molecular simulation of a coarse-grained model and theoretical arguments we envisaged how kinesin, a prototype of biological machines, generates force and regulates its dynamics to sustain persistent motor action. A structure based model, which can be versatile in adapting its structure to external stresses while maintaining its native fold, was employed to account for several features of kinesin dynamics along the biochemical cycle. This analysis complements our current understandings of kinesin dynamics and connections to experiments. We propose a thermodynamic cycle for kinesin that emphasizes the mechanical and regulatory role of the neck-linker and clarify issues related the motor directionality, and the difference between the external stalling force and the internal tension responsible for the head-head coordination. The comparison between the thermodynamic cycle of kinesin and macroscopic heat engines highlights the importance of structural change as the source of work production in biomolecular machines.

physics.bio-ph↗

arXiv2009

Dodging the crisis of folding proteins with knots

Proteins with nontrivial topology, containing knots and slipknots, have the ability to fold to their native states without any additional external forces invoked. A mechanism is suggested for folding of these proteins, such as YibK and YbeA, which involves an intermediate configuration with a slipknot. It elucidates the role of topological barriers and backtracking during the folding event. It also illustrates that native contacts are sufficient to guarantee folding in around 1-2% of the simulations, and how slipknot intermediates are needed to reduce the topological bottlenecks. As expected, simulations of proteins with similar structure but with knot removed fold much more efficiently, clearly demonstrating the origin of these topological barriers. Although these studies are based on a simple coarse-grained model, they are already able to extract some of the underlying principles governing folding in such complex topologies.

q-bio.BM↗

arXiv2009

Jamming proteins with slipknots and their free energy landscape

Theoretical studies of stretching proteins with slipknots reveal a surprising growth of their unfolding times when the stretching force crosses an intermediate threshold. This behavior arises as a consequence of the existence of alternative unfolding routes that are dominant at different force ranges. Responsible for longer unfolding times at higher forces is the existence of an intermediate, metastable configuration where the slipknot is jammed. Simulations are performed with a coarsed grained model with further quantification using a refined description of the geometry of the slipknots. The simulation data is used to determine the free energy landscape (FEL) of the protein, which supports recent analytical predictions.

q-bio.BM↗

arXiv2009

Kinesin's backsteps under mechanical load

Kinesins move processively toward the plus end of microtubules by hydrolyzing ATP for each step. From an enzymatic perspective, the mechanism of mechanical motion coupled to the nucleotide chemistry is often well explained using a single-loop cyclic reaction. However, several difficulties arise in interpreting kinesin's backstepping within this framework, especially when external forces oppose the motion of kinesin. We review evidence, such as an ATP-independent stall force and a slower cycle time for backsteps, that has emerged to challenge the idea that kinesin backstepping is due to ATP synthesis, i.e., the reverse cycle of kinesin's forward-stepping chemomechanics. Supplementing the conventional single-loop chemomechanics with routes for ATP-hydrolyzing backward steps and nucleotide-free steps, especially under load, gives a better physical interpretation of the experimental data on backsteps.

physics.bio-ph↗

arXiv2007

Mechanical control of the directional stepping dynamics of the kinesin motor

Among the multiple steps constituting the kinesin's mechanochemical cycle, one of the most interesting events is observed when kinesins move an 8-nm step from one microtubule (MT)-binding site to another. The stepping motion that occurs within a relatively short time scale (~100 microsec) is, however, beyond the resolution of current experiments, therefore a basic understanding to the real-time dynamics within the 8-nm step is still lacking. For instance, the rate of power stroke (or conformational change), that leads to the undocked-to-docked transition of neck-linker, is not known, and the existence of a substep during the 8-nm step still remains a controversial issue in the kinesin community. By using explicit structures of the kinesin dimer and the MT consisting of 13 protofilaments (PFs), we study the stepping dynamics with varying rates of power stroke (kp). We estimate that 1/kp <~ 20 microsec to avoid a substep in an averaged time trace. For a slow power stroke with 1/kp>20 microsec, the averaged time trace shows a substep that implies the existence of a transient intermediate, which is reminiscent of a recent single molecule experiment at high resolution. We identify the intermediate as a conformation in which the tethered head is trapped in the sideway binding site of the neighboring PF. We also find a partial unfolding (cracking) of the binding motifs occurring at the transition state ensemble along the pathways prior to binding between the kinesin and MT.

cond-mat.soft↗

arXiv2005

Absolute Rate Theories of Epigenetic Stability

Spontaneous switching events in most characterized genetic switches are rare, resulting in extremely stable epigenetic properties. We show how simple arguments lead to theories of the rate of such events much like the absolute rate theory of chemical reactions corrected by a transmission factor. Both the probability of the rare cellular states that allow epigenetic escape, and the transmission factor, depend on the rates of DNA binding and unbinding events and on the rates of protein synthesis and degradation. Different mechanisms of escape from the stable attractors occur in the nonadiabatic, weakly adiabatic and strictly adiabatic regimes, characterized by the relative values of those input rates.

q-bio.MN↗