TNM

TNM models protein conformational changes by performing normal mode analysis in torsion-angle space using an elastic network model while preserving backbone covalent geometry including C(β).

Key Features:

• Elastic torsional network model: Implements an elastic network model that uses torsion angles of the protein backbone as the degrees of freedom.
• Backbone covalent geometry preservation: Maintains the covalent geometry of backbone atoms, including C(β), during normal mode analysis.
• Torsion-space low-frequency modes: Identifies low-frequency modes that are localized in torsion space but exhibit collective behavior in Cartesian space.
• Hinge-like motion modeling: Captures hinge-like motions relevant to protein flexibility and function.
• Reduced mode count compared to ANM: Requires a smaller number of normal modes than anisotropic network models (ANMs) to represent experimentally observed conformational changes.
• Mode-contribution correlation: Correlates the contribution of each normal mode to equilibrium fluctuations and to conformational transitions.
• Excess correlation metric: Defines excess correlation relative to a simple neutral model and uses its strength as an indicator of the predicted free energy barrier for conformational changes.

Scientific Applications:

• Protein dynamics analysis: Analysis and prediction of protein conformational changes and flexibility.
• Hinge-motion identification: Identification and characterization of hinge-like motions in proteins.
• Experimental conformational-change representation: Representation of experimentally observed conformational transitions with a reduced set of normal modes.
• Free energy barrier inference: Inference of relative free energy barriers for conformational changes using excess correlation.

Methodology:

Uses an elastic network model in torsion-angle space and performs normal mode analysis while preserving backbone covalent geometry including C(β); defines excess correlation relative to a simple neutral model and identifies low-frequency torsion-space modes with collective Cartesian behavior.