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MoDyGAN: Combining Molecular Dynamics With GANs to Investigate Protein Conformational Space
Authors:
Jingbo Liang,
Bruna Jacobson
Abstract:
Extensively exploring protein conformational landscapes remains a major challenge in computational biology due to the high computational cost involved in dynamic physics-based simulations. In this work, we propose a novel pipeline, MoDyGAN, that leverages molecular dynamics (MD) simulations and generative adversarial networks (GANs) to explore protein conformational spaces. MoDyGAN contains a gene…
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Extensively exploring protein conformational landscapes remains a major challenge in computational biology due to the high computational cost involved in dynamic physics-based simulations. In this work, we propose a novel pipeline, MoDyGAN, that leverages molecular dynamics (MD) simulations and generative adversarial networks (GANs) to explore protein conformational spaces. MoDyGAN contains a generator that maps Gaussian distributions into MD-derived protein trajectories, and a refinement module that combines ensemble learning with a dual-discriminator to further improve the plausibility of generated conformations. Central to our approach is an innovative representation technique that reversibly transforms 3D protein structures into 2D matrices, enabling the use of advanced image-based GAN architectures. We use three rigid proteins to demonstrate that MoDyGAN can generate plausible new conformations. We also use deca-alanine as a case study to show that interpolations within the latent space closely align with trajectories obtained from steered molecular dynamics (SMD) simulations. Our results suggest that representing proteins as image-like data unlocks new possibilities for applying advanced deep learning techniques to biomolecular simulation, leading to an efficient sampling of conformational states. Additionally, the proposed framework holds strong potential for extension to other complex 3D structures.
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Submitted 18 July, 2025;
originally announced July 2025.
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Impacts of Social Distancing Policies on Mobility and COVID-19 Case Growth in the US
Authors:
Gregory A. Wellenius,
Swapnil Vispute,
Valeria Espinosa,
Alex Fabrikant,
Thomas C. Tsai,
Jonathan Hennessy,
Andrew Dai,
Brian Williams,
Krishna Gadepalli,
Adam Boulanger,
Adam Pearce,
Chaitanya Kamath,
Arran Schlosberg,
Catherine Bendebury,
Chinmoy Mandayam,
Charlotte Stanton,
Shailesh Bavadekar,
Christopher Pluntke,
Damien Desfontaines,
Benjamin Jacobson,
Zan Armstrong,
Bryant Gipson,
Royce Wilson,
Andrew Widdowson,
Katherine Chou
, et al. (4 additional authors not shown)
Abstract:
Social distancing remains an important strategy to combat the COVID-19 pandemic in the United States. However, the impacts of specific state-level policies on mobility and subsequent COVID-19 case trajectories have not been completely quantified. Using anonymized and aggregated mobility data from opted-in Google users, we found that state-level emergency declarations resulted in a 9.9% reduction i…
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Social distancing remains an important strategy to combat the COVID-19 pandemic in the United States. However, the impacts of specific state-level policies on mobility and subsequent COVID-19 case trajectories have not been completely quantified. Using anonymized and aggregated mobility data from opted-in Google users, we found that state-level emergency declarations resulted in a 9.9% reduction in time spent away from places of residence. Implementation of one or more social distancing policies resulted in an additional 24.5% reduction in mobility the following week, and subsequent shelter-in-place mandates yielded an additional 29.0% reduction. Decreases in mobility were associated with substantial reductions in case growth 2 to 4 weeks later. For example, a 10% reduction in mobility was associated with a 17.5% reduction in case growth 2 weeks later. Given the continued reliance on social distancing policies to limit the spread of COVID-19, these results may be helpful to public health officials trying to balance infection control with the economic and social consequences of these policies.
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Submitted 27 May, 2021; v1 submitted 21 April, 2020;
originally announced April 2020.
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Analysis of kinesin mechanochemistry via simulated annealing
Authors:
B. D. Jacobson,
L. J. Herskowitz,
S. J. Koch,
S. R. Atlas
Abstract:
The molecular motor protein kinesin plays a key role in fundamental cellular processes such as intracellular transport, mitotic spindle formation, and cytokinesis, with important implications for neurodegenerative and cancer disease pathways. Recently, kinesin has been studied as a paradigm for the tailored design of nano-bio sensor and other nanoscale systems. As it processes along a microtubule…
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The molecular motor protein kinesin plays a key role in fundamental cellular processes such as intracellular transport, mitotic spindle formation, and cytokinesis, with important implications for neurodegenerative and cancer disease pathways. Recently, kinesin has been studied as a paradigm for the tailored design of nano-bio sensor and other nanoscale systems. As it processes along a microtubule within the cell, kinesin undergoes a cycle of chemical state and physical conformation transitions that enable it to take ~100 regular 8.2-nm steps before ending its processive walk. Despite an extensive body of experimental and theoretical work, a unified microscopic model of kinesin mechanochemistry does not yet exist. Here we present a methodology that optimizes a kinetic model for kinesin constructed with a minimum of a priori assumptions about the underlying processive mechanism. Kinetic models are preferred for numerical calculations since information about the kinesin stepping mechanism at all levels, from the atomic to the microscopic scale, is fully contained within the particular states of the cycle: how states transition, and the rate constants associated with each transition. We combine Markov chain calculations and simulated annealing optimization to determine the rate constants that best fit experimental data on kinesin speed and processivity.
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Submitted 17 November, 2014;
originally announced November 2014.
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Dynamic DNA Processing: A Microcode Model of Cell Differentiation
Authors:
Barry D. Jacobson
Abstract:
A general theoretical framework is put forth to organize and understand various observed phenomena and mathematical relationships in the field of molecular biology. By modeling each cell in eukaryotic organisms as a processor having a unique set of allowed states, represented by a specific DNA sequence, we demonstrate a method by which gene expression can be regulated. As the theory is developed,…
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A general theoretical framework is put forth to organize and understand various observed phenomena and mathematical relationships in the field of molecular biology. By modeling each cell in eukaryotic organisms as a processor having a unique set of allowed states, represented by a specific DNA sequence, we demonstrate a method by which gene expression can be regulated. As the theory is developed, we suggest reasons for the complementary, quaternary (4-base) coding scheme used in most eukaryotes. A role for transposable elements is suggested, as is a role for the abundance of noncoding DNA, along with a clearly-defined method by which single nucleotide polymorphisms (SNP's) may alter gene expression. The effect of various errors is considered. Finally, a mechanism for inter-processor communication is proposed to explain cell-cell recognition processes, which leads to an elucidation of a possible pathway by which nonmutagenic carcinogenic agents may act.
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Submitted 17 December, 2013;
originally announced December 2013.