Computational methods in physical virology: a critical perspective across lengths and timescales.

چکیده اصلی

Physical virology investigates viral particles by focusing on their assembly, stability, mechanics, and interactions with host cells, neutralizing antibodies, and surfaces. Within this field, computational virology is becoming an indispensable pillar, serving as a "computational microscope" that bridges the spatio-temporal scales of viral processes, from individual protein dynamics to capsid assembly and cellular entry. This perspective article offers a critical overview of the current state, challenges, and future directions of computational approaches in physical virology. Our vision is anchored in the research presented at the 2025 EMBO/FEBS Lecture Course on Physical Virology held in Sant Feliu de Guixols, Spain, and complemented by a targeted survey among attendees. We survey the principal methodological frameworks in use, from all-atom to multiscale molecular simulations, mesoscale simulations, and growing integration of artificial intelligence (AI) tools. We also critically examine the central obstacles impeding the field's progress, including the computational-experimental gap, limited accessibility to simulation data, reproducibility concerns, and systemic gender and geographic inequities. Finally, we outline future perspectives, proposing that integrating physics-aware AI with multiscale simulation frameworks, combined with community-driven data-sharing initiatives, will transform the computational microscope from a descriptive tool into a predictive engine for antiviral therapies, rational vaccine design, and biotechnological innovation.

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