Molecular Modeling and Simulations of Biologics

Molecular dynamics (MD) simulations are widely used in computational and structural biology to study the time-dependent behavior of biological macromolecules at atomic resolution. Over the years, they have become an indispensable tool in the study of biomolecular systems and have been applied to investigate protein folding, conformational change, ligand interaction, protein structure determination, and refinement of X-ray crystallographic models. This chapter presents a practical, end-to-end protocol for performing MD simulations on large biomolecules, using a full-length antibody as a case study. It also introduces foundational software tools commonly used in molecular modeling and MD simulations, including PyMOL, visual molecular dynamics (VMD), nanoscale molecular dynamics (NAMD), MDAnalysis, and others. Additionally, the protocol covers the modeling of antibody-excipient interactions and identifying binding sites from MD trajectories. Together, this accessible and reproducible framework aims to equip researchers with the computational tools and foundational knowledge needed to study the dynamic behavior of complex biomolecular systems and integrate MD simulations into their own biological research.