Efficient sampling of conformational space via unbiased molecular dynamics in multiple low-dimensional collective variable spaces

Efficient sampling of conformational space via unbiased molecular dynamics in multiple low-dimensional collective variable spaces | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Efficient sampling of conformational space via unbiased molecular dynamics in multiple low-dimensional collective variable spaces Wentao zhu, Wenfei Li, Bing Bu, Linlin Zhu, Xiang Wang, Linhong Deng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6157888/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Molecular dynamics (MD) simulations struggle to resolve rare conformational transitions hindered by high energy barriers. We introduce the Equivalent Weight Method (EWM), an enhanced sampling framework that combines dynamic trajectory segmentation and adaptive weight balancing guided by real-time density analysis. EWM enables comprehensive conformational exploration by strategically combining multiple low-dimensional collective variable (CV) spaces with real-time CV augmentation. Validated across model potentials and a coarse-grained calmodulin system, EWM demonstrates marked efficiency gains over conventional MD simulations, while preserving the system's natural thermodynamic and kinetic properties. This approach circumvents the limitations of fixed high-dimensional CV representations, offering a robust balance between computational efficiency and physical accuracy. Physical sciences/Mathematics and computing/Computational science Biological sciences/Biophysics/Computational biophysics Physical sciences/Chemistry/Chemical biology/Computational chemistry Physical sciences/Physics/Statistical physics, thermodynamics and nonlinear dynamics/Statistical physics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SI.docx Supplemental Materials Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6157888","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":426645962,"identity":"2420c36a-5378-45a5-a13c-9b3e3594d749","order_by":0,"name":"Wentao 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