Minimal Collective Variables for Conformational Transitions in Steered and Temperature-Accelerated MD Simulations: A T4 Lysozyme Case Study.

ABSTRACT: Conformational transitions in proteins can be difficult to observe with equilibrium molecular dynamics and challenging for enhanced sampling methods like Targeted MD when high-resolution structural data are unavailable. Low-resolution data, such as interatomic distances and angles, can serve as collective variables (CVs) to bias steered MD (SMD) simulations, but the optimal choice and number of CVs remain unclear. Here, we identify a minimal set of CVs that drive successful transitions between metastable states in T4 lysozyme. We validate them using temperature-accelerated MD (TAMD) to accelerate conformational changes in the absence of target bias. We found that CVs at both the largest and smallest scales are necessary, including interdomain hinge bending and local side-chain reorientatio

SUBMITTER: Abou-Hatab S 

PROVIDER: S-EPMC12128028 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature