scholarly journals Multi-Scale Coarse Grained Model for the Stepping of Molecular Motors with application to Kinesin.

2021 ◽  
Author(s):  
Yonathan Y Goldtzvik ◽  
D Thirumalai
Keyword(s):  
Molecular Motors ◽  
Interaction Strength ◽  
Accurate Method ◽  
Significant Loss ◽  
Coarse Grained ◽  
Power Stroke ◽  
Coarse Grained Model ◽  
Multi Scale ◽  
Walking Mechanism ◽  
Conventional Kinesin

Conventional kinesin, a motor protein that transports cargo within cells, walks by taking multiple steps towards the plus end of the microtubule (MT). While significant progress has been made in understanding the details of the walking mechanism of kinesin there are many unresolved issues. From a computational perspective, a central challenge is the large size of the system, which limits the scope of time scales accessible in standard computer simulations. Here, we create a general multi-scale coarse-grained model for motors that enables us to simulate the stepping process of motors on polar tracks (actin and MT) with focus on kinesin. Our approach greatly shortens the computation times without a significant loss in detail, thus allowing us to better describe the molecular basis of the stepping kinetics. The small number of parameters, which are determined by fitting to experimental data, allows us to develop an accurate method that may be adopted to simulate stepping in other molecular motors. The model enables us to simulate a large number of steps, which was not possible previously. We show in agreement with experiments that due to the docking of the neck linker (NL) of kinesin, sometimes deemed as the power stroke, the space explored diffusively by the tethered head is severely restricted allowing the step to be in a tens of microseconds. We predict that increasing the interaction strength between the NL and the motor head, achievable by mutations in the NL, decreases the stepping time but reaches a saturation value. Furthermore, the full 3-dimensional dynamics of the cargo are fully resolved in our model, contributing to the predictive power and allowing us to study the important aspects of cargo-motor interactions.

Multi-scale simulations of biological systems using the OPEP coarse-grained model

2018 ◽  
Vol 498 (2) ◽  
pp. 296-304 ◽  
Author(s):  
Fabio Sterpone ◽  
Sébastien Doutreligne ◽  
Thanh Thuy Tran ◽  
Simone Melchionna ◽  
Marc Baaden ◽  
...  
Keyword(s):  
Biological Systems ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Multi Scale

scholarly journals Importance of Interface in the Coarse-Grained Model of CNT /Epoxy Nanocomposites

Nanomaterials ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 1479 ◽  
Author(s):  
Ke Duan ◽  
Li Li ◽  
Fei Wang ◽  
Weishuang Meng ◽  
Yujin Hu ◽  
...  
Keyword(s):  
Polymer Nanocomposites ◽  
Cohesive Energy ◽  
Load Transfer ◽  
Interaction Strength ◽  
Coarse Graining ◽  
Thermomechanical Properties ◽  
Coarse Grained ◽  
Strength Parameter ◽  
Coarse Grained Model ◽  
Transfer Behavior

Interface interactions play a crucial role in determining the thermomechanical properties of carbon nanotubes (CNTs)/polymer nanocomposites. They are, however, poorly treated in the current multi-scale coarse-grained (CG) models. To develop suitable CG models of CNTs/polymer nanocomposites, we demonstrate the importance of two aspects for the first time, that is, preserving the interfacial cohesive energy and reproducing the interface load transfer behavior of all-atomistic (AA) systems. Our simulation results indicate that, for CNTs/polymer nanocomposites, the interface cohesive energy and the interface load transfer of CG models are generally inconsistent with their AA counterparts, revealing significant deviations in their predicted mechanical properties. Fortunately, such inconsistency can be “corrected” by phenomenologically adjusting the cohesive interaction strength parameter of the interface LJ potentials in conjunction with choosing a reasonable degree of coarse-graining of incorporated CNTs. We believe that the problem studied here is general for the development of the CG models of nanocomposites, and the proposed strategy used in present work may be applied to polymer nanocomposites reinforced by other nanofillers.

scholarly journals Kinematics of the lever arm swing in myosin VI

2017 ◽  
Vol 114 (22) ◽  
pp. E4389-E4398 ◽  
Author(s):  
Mauro L. Mugnai ◽  
D. Thirumalai
Keyword(s):  
Rotational Diffusion ◽  
Quantitative Agreement ◽  
Motor Domain ◽  
Coarse Grained ◽  
Power Stroke ◽  
Myosin Vi ◽  
Step Size ◽  
Arm Swing ◽  
Coarse Grained Model ◽  
Lever Arm

Myosin VI (MVI) is the only known member of the myosin superfamily that, upon dimerization, walks processively toward the pointed end of the actin filament. The leading head of the dimer directs the trailing head forward with a power stroke, a conformational change of the motor domain exaggerated by the lever arm. Using a unique coarse-grained model for the power stroke of a single MVI, we provide the molecular basis for its motility. We show that the power stroke occurs in two major steps. First, the motor domain attains the poststroke conformation without directing the lever arm forward; and second, the lever arm reaches the poststroke orientation by undergoing a rotational diffusion. From the analysis of the trajectories, we discover that the potential that directs the rotating lever arm toward the poststroke conformation is almost flat, implying that the lever arm rotation is mostly uncoupled from the motor domain. Because a backward load comparable to the largest interhead tension in a MVI dimer prevents the rotation of the lever arm, our model suggests that the leading-head lever arm of a MVI dimer is uncoupled, in accord with the inference drawn from polarized total internal reflection fluorescence (polTIRF) experiments. Without any adjustable parameter, our simulations lead to quantitative agreement with polTIRF experiments, which validates the structural insights. Finally, in addition to making testable predictions, we also discuss the implications of our model in explaining the broad step-size distribution of the MVI stepping pattern.

scholarly journals Non-equilibrium effects of molecular motors on polymers

Soft Matter ◽  
2019 ◽  
Vol 15 (29) ◽  
pp. 5995-6005 ◽  
Author(s):  
M. Foglino ◽  
E. Locatelli ◽  
C. A. Brackley ◽  
D. Michieletto ◽  
C. N. Likos ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Molecular Motors ◽  
Coarse Grained ◽  
Polymer Substrates ◽  
Coarse Grained Model ◽  
Non Equilibrium

We present a generic coarse-grained model to describe molecular motors acting on polymer substrates, mimicking, for example, RNA polymerase on DNA or kinesin on microtubules.

scholarly journals Derivation of coarse-grained simulation models of chlorophyll molecules in lipid bilayers for applications in light harvesting systems

2015 ◽  
Vol 17 (34) ◽  
pp. 22054-22063 ◽  
Author(s):  
Ananya Debnath ◽  
Sabine Wiegand ◽  
Harald Paulsen ◽  
Kurt Kremer ◽  
Christine Peter
Keyword(s):  
Lipid Bilayers ◽  
Light Harvesting ◽  
Simulation Models ◽  
Coarse Grained ◽  
Light Harvesting Complex ◽  
Green Plants ◽  
Coarse Grained Model ◽  
Multi Scale ◽  
Harvesting Systems ◽  
Association Behavior

A coarse-grained model is derived for chlorophyll molecules in lipid bilayers using a multi-scale simulation ansatz aiming to understand the association behavior of the light harvesting complex (LHCII) of green plants.

scholarly journals On the Importance of Hydrodynamic Interactions in the Stepping Kinetics of Kinesin

2016 ◽  
Author(s):  
Dave Thirumalai ◽  
Yonathan Goldtzvik ◽  
Zhechun Zhang
Keyword(s):  
Coiled Coil ◽  
Quantitative Agreement ◽  
Single Step ◽  
Hydrodynamic Interactions ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Target Binding ◽  
Conventional Kinesin ◽  
Kinetics Of ◽  
Target Binding Site

Conventional kinesin walks by a hand-over-hand mechanism on the microtubule (MT) by taking ∼ 8nmdiscrete steps, and consumes one ATP molecule per step. The time needed to complete a single step is on the order of twenty microseconds. We show, using simulations of a coarse-grained model of the complex containing the two motor heads, the MT, and the coiled coil that in order to obtain quantitative agreement with experiments for the stepping kinetics hydrodynamic interactions (HI) have to be included. In simulations without hydrodynamic interactions spanning nearly twenty microseconds not a single step was completed in hundred trajectories. In sharp contrast, nearly 14% of the steps reached the target binding site within 6 microseconds when HI were included. Somewhat surprisingly, there are qualitative differences in the diffusion pathways in simulations with and without HI. The extent of movement of the trailing head of kinesin on the MT during the diffusion stage of stepping is considerably greater in simulations with HI than in those without HI. Our results suggest that inclusion of HI is crucial in the accurate description of motility of other motors as well.

scholarly journals Dynamics of Allosteric Transitions in Dynein

2018 ◽  
Author(s):  
Yonathan Goldtzvik ◽  
Mauro L. Mugnai ◽  
D. Thirumalai
Keyword(s):  
Conformational Changes ◽  
Cytoplasmic Dynein ◽  
Motor Domain ◽  
Coarse Grained ◽  
Power Stroke ◽  
Coarse Grained Model ◽  
Multiple Routes ◽  
Adp Release ◽  
Mechanical Element ◽  
Allosteric Transitions

1SummaryCytoplasmic Dynein, a motor with an unusual architecture made up of a motor domain belonging to the AAA+ family, walks on microtubule towards the minus end. Prompted by the availability of structures in different nucleotide states, we performed simulations based on a new coarse-grained model to illustrate the molecular details of the dynamics of allosteric transitions in the motor. The simulations show that binding of ATP results in the closure of the cleft between the AAA1 and AAA2, which in turn triggers conformational changes in the rest of the motor domain, thus poising dynein in the pre-power stroke state. Interactions with the microtubule, which are modeled implicitly, substantially enhances the rate of ADP release, and formation of the post-power stroke state. The dynamics associated with the key mechanical element, the linker (LN) domain, which changes from a straight to a bent state and vice versa, are highly heterogeneous suggestive of multiple routes in the pre power stroke to post power stroke transition. We show that persistent interactions between the LN and the insert loops in the AAA2 domain prevent the formation of pre-power stroke state when ATP is bound to AAA3, thus locking dynein in a non-functional repressed state. Motility in such a state may be rescued by applying mechanical force to the LN domain. Taken together, these results show how the intricate signaling dynamics within the motor domain facilitate the stepping of dynein.

scholarly journals Procedure to construct a multi-scale coarse-grained model of DNA-coated colloids from experimental data

Soft Matter ◽  
2013 ◽  
Vol 9 (30) ◽  
pp. 7342 ◽  
Author(s):  
Bianca M. Mladek ◽  
Julia Fornleitner ◽  
Francisco J. Martinez-Veracoechea ◽  
Alexandre Dawid ◽  
Daan Frenkel
Keyword(s):  
Experimental Data ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Multi Scale

scholarly journals Optimizing Gō-MARTINI Coarse-Grained Model for F-BAR Protein on Lipid Membrane

2021 ◽  
Vol 8 ◽  
Author(s):  
Md. Iqbal Mahmood ◽  
Adolfo B. Poma ◽  
Kei-ichi Okazaki
Keyword(s):  
Structural Changes ◽  
Lipid Membrane ◽  
Interaction Strength ◽  
Md Simulations ◽  
Coarse Grained ◽  
Lateral Interaction ◽  
Attractive Alternative ◽  
Elastic Network Model ◽  
Coarse Grained Model ◽  
Definition Of

Coarse-grained (CG) molecular dynamics (MD) simulations allow us to access much larger length and time scales than atomistic MD simulations, providing an attractive alternative to the conventional simulations. Based on the well-known MARTINI CG force field, the recently developed Gō-MARTINI model for proteins describes large-amplitude structural dynamics, which has not been possible with the commonly used elastic network model. Using the Gō-MARTINI model, we conduct MD simulations of the F-BAR Pacsin1 protein on lipid membrane. We observe that structural changes of the non-globular protein are largely dependent on the definition of the native contacts in the Gō model. To address this issue, we introduced a simple cutoff scheme and tuned the cutoff distance of the native contacts and the interaction strength of the Lennard-Jones potentials in the Gō-MARTINI model. With the optimized Gō-MARTINI model, we show that it reproduces structural fluctuations of the Pacsin1 dimer from atomistic simulations. We also show that two Pacsin1 dimers properly assemble through lateral interaction on the lipid membrane. Our work presents a first step towards describing membrane remodeling processes in the Gō-MARTINI CG framework by simulating a crucial step of protein assembly on the membrane.

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