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Complex molecular assemblies with stress-induced DNA studied via multi-scale simulations


DNA rarely exists as a relaxed linear molecule: bending and torsional deformations of DNA often happen in a cell and are essential for various biological functions. Therefore, study of structure and dynamics of stress-induced DNA conformations is an important part in biological and pharmacological sciences. In this work we develop a multi-scale modeling approach that combines atomistic and elastic rod models and thus, enables simulations of complex molecular assemblies on large time/length scales with atomistic details. A hybrid modeling approach is then employed to simulate three high-impact example systems containing unusual stress-induced DNA conformations. First, we focus our attention on describing dynamical properties of an intriguing donut-like (commonly referred to as a toroid) DNA motif recently found in bacteriophage φ29 and simulating viral DNA ejection from φ29. Next, we examine intrinsic flexibility in tightly curved DNA minicircles. Finally, we aim to characterize the transcription process on bent and twisted DNA and establish the structure-function relationship between the DNA template mechanics and the main transcription catalyst, the RNA polymerase. The study of either mechanism is of a great medical importance; transcriptional deregulation is a common feature of numerous physiological disorders (various types of cancer, neurological and rheumatic diseases, etc.) while viral infections can cause illnesses as minor as the common cold and as severe as AIDS. One of the greatest challenges in medical genetics is to determine how we can control these diseases on a molecular level. By exploring the molecular mechanisms underlying these disorders, our analysis provides an important and influential step towards our path from genetics to improvements in human healthcare.

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